bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Simulations of Peptide Inhibitors Complexed With Trypanosoma cruzi Trypanothione Reductase
Authors: Da Rocha Pita Samuel Silva , Batista Paulo Ricardo , Albuquerque Magaly Girão , Pascutti Pedro Geraldo
Published: June 2012

The drugs against tropical neglected diseases, especially Chagas’ Disease, were launched more than 30 years ago, and the development of resistance requires the discovery of new and more effective chemotherapeutic agents. Trypanosoma cruzi has a redox enzyme called trypanothione reductase which was successfully inhibited for peptide derivatives (McKie et al., Amino Acids, 2001, 20: 145). This work aims at studying the mechanism of inhibition of this enzyme through molecular dynamics simulations and evaluating the behavior of some derivatives when inhibiting this protein. We should affirm that any particular molecular dynamics analysis tools (Hbond pattern, 3‐D root‐mean‐square deviation, solvent accessible surface area, etc.) cannot be used apart from the others to justify completely these peptides inhibitory patterns. Based on our results, we reproduced the experimental data and, moreover, we discriminated against a new site in enzyme aperture, which can assist the development of powerful inhibitors against trypanothione reductase enzyme.
Design, Synthesis, Antibacterial Activity, and Molecular Docking Studies of Novel Hybrid 1,3‐Thiazine‐1,3,5‐Triazine Derivatives as Potential Bacterial Translation Inhibitor
Authors: Singh Udaya P. , Pathak Manish , Dubey Vaibhav , Bhat Hans R. , Gahtori Prashant , Singh Ramendra K.
Published: June 2012

Some novel hybrid 1,3‐thiazine‐1,3,5‐triazine derivatives were synthesized and tested for antibacterial activity. Compounds 8c and 8f were found active against Gram positive and Gram negative microorganisms. Molecular docking studies have been performed on eubacterial ribosomal decoding A site (Escherichia coli 16S rRNA A site) to rationalize the probable mode of action, binding affinity, and orientation of the molecules at the active site of receptor. The structures of all these newly synthesized compounds were confirmed by their elemental analyses and spectral data techniques viz. IR, 1H NMR, 13C NMR, and mass.
Determination of Total Sulfur in Fifteen Geological Materials Using Inductively Coupled Plasma‐Optical Emission Spectrometry (ICP‐OES) and Combustion/Infrared Spectrometry
Authors: Ackerman Lukáš , Rohovec Jan , Šebek Ondřej
Published: June 2012

A method for the determination of total sulfur in geological materials by inductively coupled plasma‐optical emission spectrometry (ICP‐OES) is described. We show that good results were obtained using this method even for sample types with very low (< 20 μg g−1) sulfur concentration (e.g., peridotite). Sulfur was determined in fifteen geological reference materials with different sulfur contents. For reference materials with certified sulfur contents, the ICP‐OES method gave results in excellent agreement with certified values, and uncertainties better than 4% RSD. ICP‐OES results for sulfur in other reference materials yielded RSDs better than 10%, where S concentrations were > 100 μg g−1 (except for diabase W‐2a, 16% RSD). Reference materials with lower sulfur contents (< 40 μg g−1) showed much higher RSDs (17–18%). Except for RMs with certified values for sulfur, most data obtained by the combustion infrared detection method generally showed higher concentrations than those measured by ICP‐OES and a better RSD (≤ 8% for all materials except DTS‐2b).
DNA Methylation Inhibitors, 5‐azacytidine and Zebularine Potentiate the Transdifferentiation of Rat Bone Marrow Mesenchymal Stem Cells into Cardiomyocytes
Authors: Naeem Nadia , Haneef Kanwal , Kabir Nurul , Iqbal Hana'a , Jamall Siddiqua , Salim Asmat
Published: June 2012

Background

Mesenchymal stem cells (MSCs) have immense self‐renewal capability. They can be differentiated into many cell types and therefore hold great potential in the field of regenerative medicine. MSCs can be converted into beating cardiomyocytes by treating them with DNA‐demethylating agents. Some of these compounds are nucleoside analogs that are widely used for studying the role of DNA methylation in biological processes as well as for the clinical treatment of leukemia and other carcinomas.

Aims

To achieve a better therapeutic option for cardiovascular regeneration, this study was carried out using MSCs treated with two synthetic compounds, zebularine and 5‐azacytidine. It can be expected that treated MSCs prior to transplantation may increase the likelihood of successful regeneration of damaged myocardium.

Methods

The optimized concentrations of these compounds were added separately into the culture medium and the treated cells were analyzed for the expression of cardiac‐specific genes by RT‐PCR and cardiac‐specific proteins by immunocytochemistry and flow cytometry. Treated MSCs were cocultured with cardiomyocytes to see the fusion capability of these cells.

Results

mRNA and protein expressions of GATA4, Nkx2.5, and cardiac troponin T were observed in the treated MSCs. Coculture studies of MSCs and cardiomyocytes have shown improved fusion with zebularine‐treated MSCs as compared to untreated and 5‐azacytidine‐treated MSCs.

Conclusion

The study is expected to put forth another valuable aspect of certain compounds, that is, induction of transdifferentiation of MSCs into cardiomyocytes. This would serve as a tool for modified cellular therapy and may increase the probability of better myocardial regeneration.
A review of volatile compounds in tektites, and carbon content and isotopic composition of moldavite glass
Authors: ŽÁK Karel , SKÁLA Roman , ŘANDA Zdeněk , MIZERA Jiří
Published: June 2012

Abstract– Tektites, natural silica‐rich glasses produced during impact events, commonly contain bubbles. The paper reviews published data on pressure and composition of a gas phase contained in the tektite bubbles and data on other volatile compounds which can be released from tektites by either high‐temperature melting or by crushing or milling under vacuum. Gas extraction from tektites using high‐temperature melting generally produced higher gas yield and different gas composition than the low‐temperature extraction using crushing or milling under vacuum. The high‐temperature extraction obviously releases volatiles not only from the bubbles, but also volatile compounds contained directly in the glass. Moreover, the gas composition can be modified by reactions between the released gases and the glass melt. Published data indicate that besides CO2 and/or CO in the bubbles, another carbon reservoir is present directly in the tektite glass. To clarify the problem of carbon content and carbon isotopic composition of the tektite glass, three samples from the Central European tektite strewn field—moldavites—were analyzed. The samples contained only 35–41 ppm C with δ13C values in the range from −28.5 to −29.9‰ VPDB. This indicates that terrestrial organic matter was a dominant carbon source during moldavite formation.
Effect of Inlet Skew on Heat/Mass Transfer From a Simulated Turbine Blade
Authors: Ghosh Kalyanjit , Goldstein R. J.
Published: June 2012

Heat (mass) transfer experiments are conducted to study the effect of an inlet skew on a simulated gas-turbine blade placed in a linear cascade. The inlet skew simulates the relative motion between rotor and stator endwalls in a single turbine stage. The transverse motion of a belt, placed parallel to and upstream of the turbine cascade, generates the inlet skew. With the freestream velocity constant at approximately 16 m/s, which results in a Reynolds number (based on the blade chord length of 0.184 m) of 1.8 × 105, a parametric study was conducted for three belt-to-freestream velocity ratios. The distribution of the Sherwood number on the suction surface of the blade shows that the inlet skew intensifies the generation of the horseshoe vortex close to the endwall region. This is associated with the development of a stronger passage vortex for a higher velocity ratio, which causes an earlier transition to turbulence. Corresponding higher mass transfer coefficients are measured between the midheight of the blade and the endwall, at a midchord downstream location. However, a negligible variation in transport properties is measured above the two-dimensional region of the blade at the higher velocity ratios. In contrast, the inlet skew has a negligible effect on the distribution of the Sherwood number on the entire pressure surface of the blade. This is mainly because the skew is directed along the passage vortex, which is from the pressure surface of the airfoil to the suction surface of the adjacent airfoil.
Fluid–Structure Interaction Using a Modal Approach
Authors: Debrabandere F. , Tartinville B. , Hirsch Ch. , Coussement G.
Published: June 2012

A new method for fluid‐structure interaction (FSI) predictions is here introduced, based on a reduced-order model (ROM) for the structure, described by its mode shapes and natural frequencies. A linear structure is assumed as well as Rayleigh damping. A two-way coupling between the fluid and the structure is ensured by a loosely coupling staggered approach: the aerodynamic loads computed by the flow solver are used to determine the deformations from the modal equations, which are sent back to the flow solver. The method is first applied to a clamped beam oscillating under the effect of von Karman vortices. The results are compared to a full-order model. Then a flutter application is considered on the AGARD wing 445.6. Finally, the modal approach is applied to the aeroelastic behavior of an axial compressor stage. The influence of passing rotor blade wakes on the downstream stator blades is investigated.
Stochastic Analysis of the Wheel-Rail Contact Friction Using the Polynomial Chaos Theory
Authors: Lee HyunWook , Sandu Corina , Holton Carvel
Published: June 2012

The coefficient of friction (CoF) is a very important factor for designing, operating, and maintaining the wheel-rail system. In the real world, accurate estimation of the CoF at the wheel-rail interface is difficult due to the effects of various uncertain parameters, e.g., wheel and rail materials, rail roughness, contact patch size, and so on. In this study, a stochastic analysis using polynomial chaos (poly-chaos) theory is performed with the newly developed 3D dry CoF model at the wheel-rail contact. The wheel-rail system is modeled as a mass-spring-damper system. Stochastic analyses with one uncertainty, combinations of two uncertainties, and a combination of three uncertainties are performed. The probability density function (PDF) results for stick CoF, slip CoF, and combined (total) CoF are presented. The stochastic analysis results show that the total CoF PDF before 1 s is dominantly affected by the stick phenomenon, whereas the slip dominantly influences the total CoF PDF after 1 s. The CoF PDFs obtained from simulations with combinations of two and three uncertain parameters have wider PDF ranges than those obtained for only one uncertain parameter. The current work demonstrates that the CoF is strongly affected by the stochastic variation of dynamic parameters. Thus, the PDF distribution of the CoF could play a very important role in the design of the wheel-rail system.
Performance and Emissions Characteristics of Bio-Diesel (B100)-Ignited Methane and Propane Combustion in a Four Cylinder Turbocharged Compression Ignition Engine
Authors: Shoemaker N. T. , Gibson C. M. , Polk A. C. , Krishnan S. R. , Srinivasan K. K.
Published: June 2012

Different combustion strategies and fuel sources are needed to deal with increasing fuel efficiency demands and emission restrictions. One possible strategy is dual fueling using readily available resources. Propane and natural gas are readily available with the current infrastructure and biodiesel is growing in popularity as a renewable fuel. This paper presents experimental results from dual fuel combustion of methane (as a surrogate for natural gas) and propane as primary fuels with biodiesel pilots in a 1.9 liter, turbocharged, 4-cylinder compression ignition engine at 1800 rev/min. Experiments were performed with different percentage energy substitutions (PES) of propane and methane and at different brake mean effective pressures (BMEP/bmep). Brake thermal efficiency (BTE) and emissions (NOx, HC, CO, CO2, O2 and smoke) were also measured. Maximum PES levels for B100-methane dual fueling were limited to 70% at 2.5 bars bmep and 48% at 10 bars bmep, and corresponding values for B100-propane dual fueling were 64% and 43%, respectively. Maximum PES was limited by misfire at 2.5 bars bmep and the onset of engine knock at 10 bars bmep. Dual fuel BTEs approached straight B100 values at 10 bars bmep while they were significantly lower than B100 values at 2.5 bars bmep. In general, dual fueling was beneficial in reducing NOx and smoke emissions by 33% and 50%, respectively, from baseline B100 levels; however, both CO and THC emissions were significantly higher than baseline B100 levels at all PES and loads.
Synthesis of Y0.2ZrXCe0.8−XO1.9 Electrolytes From the Sol-Gel Method for Intermediate Temperature URSOFC Application
Authors: Jung Guo-Bin , Jao Ting-Chu , Yeh Chia-Chen , Huang Ming-Hsien , Su Wang-Shen
Published: June 2012

A series of Y0.2ZrxCe0.8−xO1.9 compounds (0 ≤ x ≤ 0.6) had been prepared by the modified sol-gel method and characterized by powder X-ray diffraction, thermo-gravimetric analysis, four-probe resistivity, and Vickers’s hardness studies. The gels from co-precipitation were treated with heated 1-octanol. All of the samples showed fluoride structure after calcined at 600 °C. Sintering the powders of Y0.2Ce0.8O1.9 and Y0.2Zr0.6Ce0.2O1.9 at 1300 °C gave the relative density of 95.8% and 99%, respectively. 99% relative density could be obtained for all samples after sintering at 1500 °C. This study showed a much more improved result than that of the previous reports. The hardness was 13.7 GPa for the Y0.2Zr0.6Ce0.2O1.9 pellet, which was twice greater than that for Y0.2Ce0.8O1.9 (7.1 GPa). Therefore, the mechanical properties could be improved by the addition of ZrO2 to Y0.2ZrxCe0.8−xO1.9. At 800 °C, the electrical conductivity of Y0.2Ce0.8O1.9 and Y0.2Zr0.6Ce0.2O1.9 were 3.3 × 10−2 S/cm and 5.5 × 10−3 S/cm, respectively. The conductivity was decreased by the addition of ZrO2 to Y0.2Ce0.8O1.9. It showed that the conductivity and hardness of Y0.2Zr0.2Ce0.6O1.9 were 1.2 × 10−2 S/cm and 9.6 GPa, respectively, at 800 °C and could be a better electrolyte candidate for “intermediate-temperature” unitized regenerative solid oxide fuel cells.
Application of Axiomatic Design Theory to a Microfluidic Device for the Production of Uniform Water-in-Oil Microspheres Adapting an Integration Method
Authors: Song Ki-Young , Zhang Wen-Jun , Gupta Madan M.
Published: June 2012

This work describes a novel microfluidic method to generate uniform water-in-oil (W/O) microspheres using the phase separation technique. Axiomatic design theory (ADT) was employed for the conceptual design of microchannel systems, and ADT verified that the proposed microfluidic system is a decoupled design. The integration of hydrodynamic flow focusing method and crossflow method is realized in a microfluidic device with oil phase and aqueous phase. The immiscible fluids are fed by continuous air pressure. By the hydrodynamic flow focusing method, the width of the dispersed focused aqueous phase is controlled. The focused flow enters T-junction geometry downstream, and the crossflow interferes with the focused flow. By varying the applied pressure to the crossflow, the W/O microspheres are formed at the T-junction. Based on this approach, the size of the W/O microspheres can be successfully controlled from 16 μm to 35 μm in diameter within about 5% of variation. The present method has advantages such as good sphericity, few satellite droplets, active control of the microsphere diameter, and high throughput with the simple and low cost process. To achieve the promising results, this integrating method reveals high potential for production of polymer based microspheres.
Spectroscopic ellipsometry of superparamagnetic nanoparticles in thin films of poly(N-isopropylacrylamide)
Authors: Rauch Sebastian , Eichhorn Klaus-Jochen , Stamm Manfred , Uhlmann Petra
Published: June 2012

The versatility of spectroscopic Vis-ellipsometry (SE) to determine thin film properties was used to study Fe3O4-nanoparticles (NPs) embedded in thin films of poly(N-isopropylacrylamide). By using the optical constants of bulk Fe3O4 (magnetite) the volume fractions in different NP-polymer composites (0–3 vol. %) could be quantified with SE and verified with scanning electron microscopy (SEM) and atomic force microscopy. It was found that the best-fit results from SE matched well with data from SEM until 1 vol. %. The effect of the NP on the evolution of film thickness and surface morphology was analyzed. Over the whole concentration range the data obtained from SE measurements matched well with the suspended values and showed an expected linear behavior. Additionally, the optical constants (n and k) of the nanocomposites were extracted and compared to the pure polymer film. In the measured spectral range the data showed a physical meaningful behavior and the influence of the NP on the optical properties of the thin films could be observed.
Role of surface temperature in fluorocarbon plasma-surface interactions
Authors: Nelson Caleb T. , Overzet Lawrence J. , Goeckner Matthew J.
Published: June 2012

This article examines plasma-surface reaction channels and the effect of surface temperature on the magnitude of those channels. Neutral species CF4, C2F6, and C3F8 are produced on surfaces. The magnitude of the production channel increases with surface temperature for all species, but favors higher mass species as the temperature is elevated. Additionally, the production rate of CF2 increases by a factor of 5 as the surface temperature is raised from 25 °C to 200 °C. Fluorine density, on the other hand, does not change as a function of either surface temperature or position outside of the plasma glow. This indicates that fluorine addition in the gas-phase is not a dominant reaction. Heating reactors can result in higher densities of depositing radical species, resulting in increased deposition rates on cooled substrates. Finally, the sticking probability of the depositing free radical species does not change as a function of surface temperature. Instead, the surface temperature acts together with an etchant species (possibly fluorine) to elevate desorption rates on that surface at temperatures lower than those required for unassisted thermal desorption.
Nanopillar ITO electrodes via argon plasma etching
Authors: Van Dijken Jaron G. , Brett Michael J.
Published: June 2012

The authors demonstrate the formation of vertically aligned indium tin oxide (ITO) nanopillars by exposing planar ITO films to Ar plasma, the conditions of which determine the size, spacing, and aspect ratio of the pillars. Annealing in air and forming gas is used to recover and optimize the optical transmittance and electrical conductivity of the nanopillar films. The final product is an ITO film whose superior optical transmittance and strong electrical conductivity combine with its robust columnar morphology and processing scalability to make it suitable for use in highly absorbing organic solar cells.
Low-frequency resonance of an oblate spheroidal cavity in a soft elastic medium
Authors: Calvo David C. , Thangawng Abel L. , Layman Christopher N.
Published: June 2012

Axisymmetric monopole resonances of an oblate spheroidal cavity in a soft elastic medium are computed using both separation of variables and finite-element approaches. The resonances are obtained for compression wavelengths much longer than the cavity size and thus have a low-frequency character. Resonant frequencies for high-aspect-ratio oblate spheroids (either air-filled or evacuated) are found to be significantly lower than their spherical counterparts with equivalent volume. This finding contrasts with the case of an air bubble in water which features weak shape dependence. The results are relevant to the design of locally-resonant acoustic media using soft-lithography techniques with elastomers.
Single-channel dereverberation using a non-causal minimum variance distortionless response filter
Authors: Song Myung-Suk , Kang Hong-Goo
Published: June 2012

This letter presents a single-channel speech dereverberation approach using a non-causal minimum variance distortionless response (MVDR) filter. The non-causal filter is adopted to utilize the additional information of the desired signal that lies in subsequent frames. Note that the desired signal output has minimal distortion due to the introduction of the MVDR criterion. The proposed system further suppresses the late reverberation by employing a statistical reverberant model. Experimental results demonstrate the superiority of the proposed algorithm to conventional approaches.
A model for spatial coherence from directive ambient noise in attenuating, dispersive media
Authors: Walker Shane C.
Published: June 2012

As a complement to experimental efforts in seismics and acoustics to infer geo-acoustic properties of the propagation environment from the second order statistics of ambient noise measurements, a set of exact, explicit, closed form expressions for the cross-spectral density and spatial coherence of diffuse random wave fields is presented. Taken together, the expressions are well suited for modeling broadband, diffuse wave coherence in realistic scenarios involving directive, ambient noise from local (i.e., volume) and distant (i.e., plane wave) source features in an open, dispersive, attenuating medium.
Dual mechanisms in the perceptual processing of click train temporal regularity
Authors: Phillips Dennis P. , Dingle Rachel N. , Hall Susan E. , Jang Moragh
Published: June 2012

Two experiments measured human sensitivity to temporal jitter in 25-click trains with inter-click intervals (ICIs) between 5 and 100 ms. In a naturalistic experiment using wideband clicks, jitter thresholds were a nonmonotonic function of ICI, peaking for ICIs near 40–60 ms. In a subsequent experiment, clicks were high-passed and presented against a low-frequency noise masker. Jitter threshold vs ICI functions lost the positive slope over short ICIs but retained the negative slope at long ICIs. The same behavior was seen in click rate discrimination tasks. Different processes mediate regularity analysis for click trains with ICIs above and below 40–60 ms.
Vibro-acoustic response of an infinite, rib-stiffened, thick-plate assembly using finite-element analysis
Authors: Remillieux Marcel C. , Burdisso Ricardo A.
Published: June 2012

The vibration of and sound radiation from an infinite, fluid-loaded, thick-plate assembly stiffened periodically with ribs are investigated numerically using finite-element analysis. First, numerical simulations are compared to the analytical solutions presented recently for this particular problem [Hull and Welch, J. Sound Vib. 329, 4192–4211 (2010)]. It is shown that the solutions reported in this reference are partially incorrect because the number of modes was not chosen correctly. Subsequently, the numerical model is used to study the effect of repeated and equally spaced void inclusions on the vibro-acoustic response of the system.
Suppression of Immune and Hemopoietic Cellular Responses by Methisazone
Authors: McNeill T. A. , Fleming W. A. , McClure Sheena F. , Killen M.
Published: June 2012

The antiviral drug methisazone (
N
-methylisatin β-thiosemicarbazone) was tested for its effect on immune responses to sheep erythrocytes and on hemopoietic colony-forming cell (granulocyte-macrophage progenitor cell) responses to complete Freund's adjuvant in mice. Suppressive activity was demonstrated in both systems, the immune system being more readily and more consistently susceptible. Evidence is presented which suggests that the insoluble particulate form of the drug has both stimulatory and suppressive effects on the colony-forming cell system, whereas the soluble form is only suppressive. Methisazone increased the mortality from ectromelia in adjuvant-treated animals.
Antibiotic Synergism Against
Listeria monocytogenes
Authors: Moellering Robert C. , Medoff Gerald , Leech Irene , Wennersten Christine , Kunz Lawrence J.
Published: June 2012

The effectiveness of ampicillin, penicillin, streptomycin, and gentamicin against 20 strains of
Listeria monocytogenes
was studied in vitro. For all strains, the minimal bactericidal concentration (MBC) of both ampicillin and penicillin was much higher than the minimal inhibitory concentration (MIC). The MBC of both streptomycin and gentamicin was close to the MIC, but relatively high concentrations of these antibiotics were necessary to inhibit the growth of most of the strains of
Listeria
. The combination of penicillin plus streptomycin was synergistic against 19 of 20 strains and in the remaining strain produced enhanced killing (but of less magnitude than our criterion for synergism). Combinations of penicillin plus gentamicin, ampicillin plus streptomycin, and ampicillin plus gentamicin produced enhanced killing against all strains tested. No antagonism was observed when ampicillin or penicillin was combined with streptomycin or gentamicin.
Purification and Characteristics of Pyocin B39 II. Physical and Chemical Properties
Authors: Chen Chi-Pien , Tai Fu-Hsiang
Published: June 2012

A purified preparation of pyocin B39 was shown to be homogeneous by disc electrophoresis and ultracentrifugation. Pyocin B39 is an antibacterial agent, protein in nature, and is capable of inhibiting the growth of susceptible cells. It caused a susceptible strain of
Pseudomonas aeruginosa
to release ultraviolet-absorbing material. Pyocin B39 appears to be a protein with a high molecular weight; its sedimentation coefficient is 32.8
S
. It was destroyed by 7
m
urea but was resistant to attack by proteolytic enzymes, such as pepsin and trypsin. From its sedimentation coefficient, a molecular weight of about 2 × 10
6
was calculated. An electron photomicrograph of pyocin B39 revealed it as a rodlike particle, 7.50 pm long and 1.08 pm wide, with striations running at nearly right angles to the axes of the particle.
R Factor-Mediated Antibiotic Resistance in
Serratia marcescens
Authors: Cooksey Robert C. , Thorne Grace M. , Farrar W. Edmund
Published: June 2012

Nineteen of 39 multiresistant strains of
Serratia marcescens
isolated from clinical sources transferred antibiotic resistance to
Escherichia coli
or
Klebsiella pneumoniae
recipients. Marcesins and/or phage prevented effective resistance transfer to
E. coli
and attempts to select marcescin-resistant mutants of the
E. coli
recipient strain were unsuccessful. Transfer of resistance was demonstrated for all drugs tested except nalidixic acid. Approximately 90% of donors resistant to tobramycin, ampicillin, or carbenicillin transferred resistance to these drugs. High levels of transferred resistance (minimal inhibitory concentration, >2,500 μg/ml) were demonstrated particularly for ampicillin, carbenicillin, and kanamycin. Transmissibility of
Serratia
R factors was greatest between isogeneic strains of
E. coli
K-12. Comparative rates of spontaneous loss of R factor-mediated resistance indicated that
Serratia
R factors are less stable in
E. coli
and
K. pneumoniae
transcipients than in the indigenous hosts.
Antimicrobial Susceptibility of Group B Streptococci Isolated from a Variety of Clinical Sources
Authors: Baker Carol J. , Webb Bette J. , Barrett Fred F.
Published: June 2012

The minimal inhibitory concentration of 10 antibiotics for 244 isolates of group B streptococci was determined. Susceptibility to penicillin G, ampicillin, cephalothin, chloramphenicol, and carbenicillin was uniform. Tetracycline and bacitracin resistance among these isolates was frequent (87.5 and 97.9%, respectively). Three strains (1.2%) failed to be inhibited by 100 μg of lincomycin or clindamycin per ml. Susceptibility of these 244 strains to the agents tested was unrelated to source of the isolate, year of isolation, or strain serotype. No apparent change in the suceptibility of group B streptococci to penicillin G has occurred during the past 2 decades.
Bioevaluation of the Antibacterial Flumequine for Urinary Tract Use
Authors: Rohlfing S. R. , Gerster J. F. , Kvam D. C.
Published: June 2012

The antimicrobial activity of flumequine (R-802) was characterized by in vitro and in vivo procedures. Assay of the minimal inhibitory concentrations for 321 recent clinical isolates revealed that 88% of the gram-negative bacteria were inhibited by an R-802 concentration of 6.2 μg/ml or less. Cross-resistance in laboratory-derived mutants of
Proteus vulgaris
was essentially complete for R-802, nalidixic acid, and oxolinic acid, although quantitative differences were evident. R-802 was more effective than either of these quinolone antibacterials in preventing the development of experimental murine pyelonephritis (
P. vulgaris
). R-802 and trimethoprim/sulfamethoxazole (1:5) were equally effective in resolving a
P. mirabilis
-induced prostatitis of rats.
A New Cephalosporin with a Dual Mode of Action
Authors: O'Callaghan Cynthia H. , Sykes R. B. , Staniforth Susan E.
Published: June 2012

A cephalosporin, (6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-3-(pyrid-2-yl-
N
-oxide) thiomethylceph-3-em-4-carboxylic acid (MCO), that could lead to a novel approach to the problem of β-lactamase destruction is described. The compound is slightly more resistant to some β-lactamases than is cephalothin, but it is still hydrolyzed by many to a varying degree. Hydrolysis of the β-lactam bond of a cephalosporin releases the 3-substituent, which in MCO is itself an antibacterial agent, 2-mercaptopyridine-
N
-oxide. Thus, MCO has a dual mode of action, and bacteria that do not produce an effective amount of a β-lactamase are inhibited by the intact cephalosporin, whereas those that do hydrolyze it are inhibited by the released antibacterial compound.
Chemical Nature of Agrocin 84 and Its Effect on a Virulent Strain of
Agrobacterium tumefaciens
Authors: McCardell Barbara A. , Pootjes C. F.
Published: June 2012

Agrocin 84, produced by
Agrobacterium radiobacter
K84, inhibited ribonucleic acid, deoxyribonucleic acid, and protein synthesis and amino acid transport in a susceptible, virulent strain of
A. tumefaciens
H-38-9. Cell motility was immediately stopped by action of the agrocin, 50% of the cells were killed within 15 min of contact, and the remainder were inhibited. Agrocin 84 is trypsin and pepsin resistant, but chemical analysis indicated a small peptide with a molecular weight of 2,500 containing six different amino acids, including nine molecules of glutamine or glutamic acid and seven molecules of serine.
Comparison of the In Vitro Activity of Several Cephalosporin Antibiotics Against Gram-Negative and Gram-Positive Bacteria Resistant to Cephaloridine
Authors: Kisch Alexander L. , Bartholomew Luanna
Published: June 2012

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 μg of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of
Streptococcus faecalis
and of methicillin-resistant
Staphylococcus aureus
. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.
Comparison of Colicins B-K260 and D-CA23: Purification and Characterization of the Colicins and Examination of Colicin Immunity in the Producing Strains
Authors: Pugsley Anthony P. , Reeves Peter
Published: June 2012

Colicins B-K260 and D-CA23 were purified by ammonium sulfate precipitation, gel filtration, and ion-exchange chromatography and were compared with respect to a number of physical and chemical properties. Both colicins were shown to be proteins and were found to have similar molecular weights, isoelectric points and amino acid compositions. The two colicins also have substantial antigenic similarities but are distinguished by the presence of non-cross-reacting antigens and by differences in stability and in sensitivity to heat and reducing conditions. In addition, strains of
Escherichia coli
K-12 producing colicins B-K260 and D-CA23 are not cross-immune. The similarities noted between the two colicins are compatible with their use of a common cell surface receptor while having different modes of action.
Effect of Ethambutol on the Viable Cell Count in
Mycobacterium smegmatis
Authors: Kilburn James O. , Greenberg Joseph
Published: June 2012

Soon after a strain of
Mycobacterium smegmatis
was exposed to ethambutol (EMB), the number of viable cells increased dramatically above the number in a drug-free control. This rapid rise did not occur when the culture was maintained at 4°C instead of 37°C, when an EMB-resistant mutant was used, when auxotrophs were exposed in medium lacking nutrients essential for growth, nor when the levo form of EMB was used. EMB caused no increase in deoxyribonucleic acid synthesis, nor in septum formation of dividing cells. Treated cells changed morphologically, resulting in a lower surface area-to-volume ratio. Whereas EMB did not eliminate cell clusters, the cluster size decreased markedly as detected by filtration and Coulter counter measurements. We concluded that EMB causes a reduced surface-to-volume ratio, leading to reduced cell cohesion and a consequent reduction in cluster size, reflected in an increase in colony-forming units.
Evaluation of the Autobac 1 Susceptibility Testing System in a Clinical Diagnostic Laboratory
Authors: Mogyoros Miguel , Morgan John R. , Smith John A.
Published: June 2012

The Autobac 1 system was compared to the disk diffusion and agar dilution methods. Overall, there was good correlation; however, certain antibiotic/bacterial combinations gave unreliable results. In particular, unreliable results were obtained against staphylococci with penicillins, aerobic gram-negative rods with cephalothin, and enterococci with cephalothin and clindamycin.
2″-
O
-Phosphorylation of Gentamicin Components by a
Staphylococcus aureus
Strain Carrying a Plasmid
Authors: Goffic F. Le , Martel A. , Moreau N. , Capmau M. L. , Soussy C. J. , Duval J.
Published: June 2012

A wild-type strain of
Staphylococcus aureus
that inactivates the 4,6-glycosidically linked deoxystreptamine aminoglycoside antibiotics by a plasmid-mediated process was found to harbor two enzymes: an acetyltransferase of the AAC(6′) type and a new phosphotranferase specific to the gentamicin components. The target of this last enzyme is the 2″-hydroxyl function of these antibiotics, since one inactivated compound is 2″-(
O
)-phosphorylsisomicin.
Cytotoxicity and Cell Cycle Specificity of Homoharringtonine
Authors: Baaske D. M. , Heinstein Peter
Published: June 2012

The plant alkaloid, homoharringtonine, isolated from
Cephalotaxus harringtonia
is cytotoxic to HeLa, KB, and L cells growing in monolayer cell cultures. This effect appears to be cell-cycle specific. In synchronized KB cells, protein synthesis was preferentially inhibited in the G
1
and G
2
phases (70 and 45% inhibition, respectively) as might be expected for a protein-synthesis inhibitor.
Binding of Thienamycin and Clavulanic Acid to the Penicillin-Binding Proteins of
Escherichia coli
K-12
Authors: Spratt Brian G. , Jobanputra Vinay , Zimmermann Willy
Published: June 2012

Thienamycin and clavulanic acid are new β-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical β-lactam antibiotics since they bound to precisely the same proteins as [
14
C]benzylpenicillin. Thienamycin showed high affinity for penicillin-binding proteins 1, 2, 4, 5, and 6 and a lower affinity for protein 3. Protein 2 had the highest affinity for thienamycin, and concentrations from the minimal morphological change concentration (0.1 μg/ml) up to about 0.6 μg/ml resulted in the conversion of
Escherichia coli
KN126 into large osmotically stable round cells. Above a concentration of 0.6 μg/ml, rapid cell lysis occurred with the release of the cell contents as spheroplasts. Clavulanic acid showed good affinity for penicillin-binding protein 2, moderate affinity for proteins 1, 4, 5, and 6, and low affinity for protein 3. Protein 2 had the highest affinity for clavulanic acid, and concentrations from the minimal morphological change concentration (30 μg/ml) up to about 50 μg/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 μg/ml, rapid lysis occurred with production of spheroplasts. The properties of thienamycin and clavulanic acid were compared with those of the penicillins, cephalosporins, and amidinopenicillanic acids.
Bacteriocin from
Actinomyces odontolyticus
with Temperature-Dependent Killing Properties
Authors: Franker Colin K. , Herbert C. Achille , Ueda Stuart
Published: June 2012

A strain of
Actinomyces odontolyticus
, originally isolated from human dental plaque, produced a non-dialyzable, trypsin-sensitive substance that was bactericidal for certain strains of bifidobacteria at 42°C but not at 37°C. Detectable quantities of the bacteriocin were not produced in liquid media. Experimentally useful yields were obtained by extraction from pour plate cultures of producer cells. At 42°C, exponential killing did not occur until indicator cells had doubled at least once. At 37°C, the bacteriocin effected a transient bacteriostasis. Partially purified concentrates were obtained by diethylaminoethyl-cellulose chromatography, and such material was not inactivated by ribonuclease, deoxyribonuclease, or lipase. Pronase, trypsin, and exposure to 100°C for 20 min completely abolished activity. Inhibitory activity was considerably reduced by exposure to a pH of either 3 or 11. Treatment of producer cells with curing agents did not induce a high frequency of non-bacteriocinogenic cells. The odontolyticin was adsorbed by susceptible, as well as resistant, bacteria.
Plasmid-Mediated Resistance to Gentamicin in
Staphylococcus aureus
Authors: Wood David O. , Carter Mary Jo , Best Gary K.
Published: June 2012

Two strains isolated from a recent outbreak of infections by gentamicin-resistant
Staphylococcus aureus
were examined to determine whether genetic control of this resistance is plasmid or chromosomally mediated. Curing techniques indicated a plasmid location in both strains. Physical isolation and characterization of the plasmid deoxyribonucleic acid from one strain revealed that the determinant for gentamicin resistance resides on a 50S plasmid.
Discrepant Results of Amphotericin B Assays on Fresh Versus Frozen Serum Samples
Authors: Bannatyne R. M. , Cheung R.
Published: June 2012

Amphotericin B assays on frozen serum samples (−20°C) generally underestimate the serum levels obtained on promptly processed samples. The degree of the discrepancy is variable and independent of the length of time stored.
Study of ansamycin inhibition of a ribonucleic acid-directed deoxyribonucleic acid polymerase by an immobilized template assay
Authors: Milavetz B I , Horoszewicz J S , Rinehart K L , Carter W A
Published: June 2012

A series of structurally related ansamycins have been analyzed, in a new immobilized template assay, to determine the mechanism by which they inhibit a ribonucleic acid-directed deoxyribonucleic acid (DNA) polymerase from Moloney murine leukemia virus. By this assay, we can better correlate specific structures of these drugs with inhibitory mechanisms. Using an immobilized template, we were also able to observe drug effects on the stability of complexes formed between the polymerase, a template (polyadenylic acid-agarose), and a primer, as well as to monitor the synthesis of DNA in the presence of drug. For each drug, we determined the complex (intermediate in DNA synthesis) which was primarily affected and whether the effect was due to a destabilization process. Although the activity and specificity of the unsubstituted ansamycins (streptovaricins and rifamycin SV) were modulated by conformation of the molecule and electron density of the aromatic ring, the principal mode of inhibition is, apparently, drug binding to a polymerase-template complex; the drug binds in a manner which prevents subsequent formation of a polymerase-template-primer complex. However, some derivatives of rifamycin SV, when substituted at carbon-3 with bulky or hydrophobic side chains, displayed markedly different modes of action. For example, demethyl dimethyl rifampin prevented the formation of polymerase-template complexes, whereas rifazacyclo 16 acted by promoting the dissociation of polymerase-template-primer complexes.
Accumulation Pharmacokinetics of Tobramycin
Authors: Schentag Jerome J. , Lasezkay George , Cumbo Thomas J. , Plaut Martin E. , Jusko William J.
Published: June 2012

Tobramycin pharmacokinetics is usually described by a one-compartment model, but this model fails to account for both the incomplete urinary recovery and prolonged post-treatment persistence noted with this drug. We examined the multiple-dose behavior of tobramycin in 35 treated patients with stable renal function, using peak and trough serum concentrations, urine recovery, and postmortem tissue analysis. Serum concentrations rose slowly throughout treatment and declined in two phases after the drug was stopped. The first-phase half-life correlated well with renal function, but the second averaged 146 h and was poorly related to creatinine clearance. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of drug in the tissue compartment at all times during and after treatment. Predicted tissue amounts rose continually throughout treatment in all study patients. In 5 patients, the total amount of tobramycin in the body after the final dose was recovered in the urine, but urine had to be collected for 10 to 20 days to achieve complete recovery of the drug. In four patients, the predicted tissue amount was recovered from postmortem tissues. Regardless of the dose, tobramycin accumulated in the tissues of all patients receiving this antibiotic. The two-compartment pharmacokinetic model explains both the rising peak and trough concentrations during treatment and the detection of the drug in serum and urine long after the last dose.
Microbial Degradation of Cephalothin by Cephalothin-Susceptible
Escherichia coli
Authors: Nishiura Tsuneo , Kawada Yukimichi , Shiomi Yoko , O'Hara Koji , Kono Megumi
Published: June 2012

Cephalothin (CET)-susceptible
Escherichia coli
, which can degrade CET after prolonged incubation in broth containing a concentration of the drug greater than the minimum inhibitory concentration, was found in a clinical specimen. The substrate specificity of the partially purified enzyme to cephalosporin analogs strongly indicated the occurrence of CET-specific degradation. Nuclear magnetic resonance analysis of the degradation reaction demonstrated the appearance of two new signals attributed to deacetyl CET. This suggests the possibility of the presence of acylesterase.
Synergistic Activity of Gentamicin with Trimethoprim or Sulfamethoxazole-Trimethoprim Against
Escherichia coli
and
Klebsiella pneumoniae
Authors: Paisley J. W. , Washington J. A.
Published: June 2012

The effect of combinations of gentamicin with trimethoprim or sulfamethoxazole-trimethoprim against clinical isolates of
Escherichia coli
(11 strains) and
Klebsiella pneumoniae
(12 strains) was examined by using a microdilution checkerboard technique. All isolates were susceptible to each antimicrobial agent. Synergism, defined as at least a 2-log
2
-dilution lowering of the minimal inhibitory concentration of either antibiotic in the combination compared with the minimal inhibitory concentration of the antibiotic alone, was observed with 15 of 23 (65%) isolates tested against trimethoprim and gentamicin and 14 of 23 (61%) isolates tested against sulfamethoxazole-trimethoprim and gentamicin. A 3-log
2
-dilution lowering of the minimal inhibitory concentration of either antibiotic was observed in 7 of 23 (30%) trimethoprim and gentamicin trials and 3 of 23 (13%) sulfamethoxazole-trimethoprim and gentamicin trials. Antagonism was observed in 3 of 46 combination trials and only with strains of
K. pneumoniae
.
Colicinogeny of
Escherichia coli
MRE 600
Authors: Salaj-Šmic Erika
Published: June 2012

Escherichia coli
MRE 600 is a colicinogenic bacterium. Its colicinogenic activity may be ascribed mostly to colicin E1, although it produces a small amount of another, as yet unidentified, colicin.
Amikacin Assay in Serum by High-Performance Liquid Chromatography
Authors: Maitra Shyamal K. , Yoshikawa Thomas T. , Steyn Catherine M. , Guze Lucien B. , Schotz Michael C.
Published: June 2012

A high-performance liquid chromatographic method for the quantitative determination of amikacin in serum is described. The antibiotic was separated from serum by adsorption on silica gel. The adsorbed drug was then derivatized with
o
-phthalaldehyde and eluted with ethanol. The derivatized amikacin was separated by reverse-phase, high-performance liquid chromatography and quantitated by fluorometry. A linear response for serum samples containing amikacin ranging from 1.0 to 15 μg/ml was obtained. Other antibiotics including various aminoglycosides did not interfere with the amikacin assay. Comparison with a standard microbiological assay gave a correlation coefficient of 0.99. This chemical assay is sensitive and specific under the conditions tested and can be performed rapidly.
Materno-Fetal Cephradine Transfer in Pregnancy
Authors: Craft Ian , Forster Thomas C.
Published: June 2012

Cephradine, a semisynthetic cephalosporin, has widespread use. There is, however, a paucity of data on the transfer of this antibiotic in pregnancy. Studies were undertaken after an intravenous dose of 2 g of cephradine was given in two elective situations: (i) therapeutic abortion in the first trimester and (ii) elective cesarean section in late pregnancy. Blood and tissue levels of cephradine obtained showed that the antibiotic is rapidly transferred to the feto-placental unit throughout pregnancy after intravenous administration to the mother.
Production of β-Lactamase by Non-
Streptomyces Actinomycetales
Authors: Schwartz Jeffrey L. , Schwartz Surya P.
Published: June 2012

Supernatants and whole cells from fermentation broths of
Micromonospora, Nocardia, Oerskovia
, and other genera of the
Actinomycetales
were examined for the presence of β-lactamase activity by using the chromogenic cephalosporin 87/312. Nearly 60% of the 250 isolates examined produced detectable levels of β-lactamase. All enzyme preparations were active over a range of pH values from 6.5 to 8.2, with maximum activity occurring between 7.0 and 7.8. The preparations varied in their stability at 60°C. An examination of selected enzyme preparations revealed a similarity between substrate specificities of the non-
Streptomyces Actinomycetales
and gram-negative-bacterial β-lactamases.