bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Response of Polyvinyl Alcohol(PVA)-Hydrogel With Different PVA Concentrations
Authors: Han Changwan , Park Seonghun , Kim Hanjong 
Published: June 2016

Polyvinyl Alcohol-Hydrogel (PVA-H) is a biomaterial used for manufacturing contact lenses as well as for the medium of drug delivery. Previous studies have also showed that PVA-H exhibits superior biocompatibility with hydrophilic elastic nature. The aim of this study is to examine the possible usage of the PVA-H as cartilage replacement material by determining the static and dynamic mechanical properties of PVA-H with different ratios of polyvinyl alcohol (PVA) and phosphate buffered saline (PBS) compositions.
Three different types of PVA-H specimens were made by changing the ratio of PVA (Sigma-Aldrich) and PBS (Sigma-Aldrich) compositions (PVA-H1: 10 wt% PVA and 90 wt% PBS; PVA-H2: 20 wt% PVA and 80 wt% PBS; PVA-H3: 25 wt% PVA, 45 wt% PBS and DMSO 30 wt%). Static and dynamic tensile tests under the loading frequencies of 0.001, 0.01, 0.1, and 1 Hz were carried out to measure the biomechanical properties of PVA-H1, -H2 within PBS solution and -H3 within PBS/ DMSO solution.
The equilibrium Young’s moduli (EY) of PVA-H1, -H2 and -H3 evaluated from the static displacement control were 84.2±35.1 kPa (n=10), 254±32.2 kPa (n=10) and 588±38.9 kPa (n=5), respectively. The amplitudes of dynamic tensile moduli were varied from 86.3±33.4 kPa (n=10) at 0.001 Hz to 96.9±42.0 kPa (n=10) at 1 Hz for PVA-H1, from 282.7±26.4 kPa (n=10) at 0.001 Hz to 309.1±32.2 kPa (n=10) at 1 Hz for PVA-H2 and from 643.8±49.8 kPa (n=10) at 0.001 Hz to 747.7±67.7 kPa (n=5) at 1 Hz for PVA-H3. According to the current results, the frequency dependence of the magnitude of the dynamic modulus confirms the viscoelastic nature of PVA-H material. However, it can be noted that the dynamic modulus increases by up to a factor of 1.15 for PVA-H1, 1.22 for PVA-H2 and 1.27 for PVA-H3, showing insignificant viscoelasticity compared with that for cartilage. The result that static and dynamic moduli of PVA-H3 are larger than those of PVA-H1 and PVA-H2 also suggests that the amount of PVA composition in PVA-H plays an important role in improving both static and dynamic mechanical strengths of PVA-H material. The phase angle decreased from 5.2±2.1 ° at 0.001 Hz to −0.3±1.7 ° at 1 Hz for PVA-H1, from 5.6±0.6 ° at 0.001 Hz to −0.3±0.7 ° at 1 Hz for PVA-H2 and from 8.2±1.1 ° at 0.001 Hz to 0.7±0.7 ° at 1 Hz for PVA-H3.
Fostering Ethical, Social, Environmental, Health, and Safety Awareness in Tomorrow’s Engineers and Technologists
Authors: Hanks J. Craig , Tate Jitendra , Fazarro Dominick , Trybula Walt , McLean Robert J. C. , Dutta Satyajit , Allhoff Fritz , Barton Seth , Russell Zach 
Published: June 2016

This paper reports on our work developing a set of modular courses to intended to help foster Ethical, Social, Environmental, Health, and Safety Awareness in Tomorrow’s Engineers and Technologists. We focus on emerging technologies, and especially nanotechnology. In the last decade nanotechnology has made myriad inroads into mainstream society. It is merely one of many exciting new ways that science and technology are changing how we live and think. Along with these developments in science and technology come new industries, and new challenges. This requires heightened awareness of health and safety risks, ethical and social considerations, and environmental implications of their work. This need is not limited to nanotechnologies, nor revolutionary technologies, but should be an integral part of all engineering work.
Our NSF-funded project is developing and introducing introductory and advanced curricula for online and face-to-face course modules taught as full courses or infused into existing courses. The courses and modules are being developed and piloted with the guidance of an advisory council made up of nanotechnology leaders from academia and industry. One important goal of the project is to recruit, engage, prepare, and encourage students from traditionally underrepresented groups to careers in Science and Engineering, with a focus on Nanotechnology.
In this paper we explain the origin of the project and how we developed the course modules, review the first semesters teaching from these modules, and examine our initial results and evaluations.
Design of New Multifunctional Galling-Corrosion Testing Apparatus
Authors: Azzi M. , Bitar-Nehme E. , Klemberg-Sapieha J. E. 
Published: June 2016

Galling of materials is a severe surface damage characterized by macroscopic material removal when two solid surfaces experience relative sliding under high load. This mode of wear is of particular interest in applications where design constraints require assembly components to slide against each other without adequate lubrication. Examples are high-pressure ball valve with metal-to-metal seal contact, sheet metal forming process and medical/food processing instruments where lubrication is sometimes non-existent due contamination concerns. In addition to sliding at high load, materials in these applications can be exposed to aggressive environments which lead to combined tribological and corrosive degradation phenomena. Progress in this field depends largely on the understanding of the interaction between corrosion and wear processes. In this paper, we describe a new testing instrument capable of testing galling and sliding wear behavior under dry and wet conditions. Design of this instrument is guided by ASTM standards G98 for galling, G99 for pin-on-disk, G133 for ball-on-flat and G199 for tribocorrosion.
Galling configuration consists of two concentrically aligned hollow cylindrical specimen loaded along their longitudinal axis with constant load (max 5000 N). The upper specimen is held stationary while the lower specimen is rotated a number of cycles at a selected speed. During the test, the friction torque is measured using special torque/thrust load cell. For the combined galling/corrosion test, the specimen’s contact surface is submerged in an electrolytic solution and three-electrode type electrochemical cell is set-up using the specimens as working electrode. Galling/corrosion tests can be performed under open circuit potential or under controlled potentials. In the first type, the corrosion potential is monitored before, during and after rubbing, whereas in the second type, the corrosion potential and corrosion current are controlled before, during and after rubbing. In addition to galling, the instrument can also be used to conduct pin-on-disk and ball-on-flat tests under dry and wet conditions.
Horizontal Transfer of Carbapenemase-Encoding Plasmids and Comparison with Hospital Epidemiology Data
Authors: Hardiman C. A. , Weingarten R. A. , Conlan S. , Khil P. , Dekker J. P. , Mathers A. J. , Sheppard A. E. , Segre J. A. , Frank K. M. 
Published: June 2016

ABSTRACT

Carbapenemase-producing organisms have spread worldwide, and infections with these bacteria cause significant morbidity. Horizontal transfer of plasmids carrying genes that encode carbapenemases plays an important role in the spread of multidrug-resistant Gram-negative bacteria. Here we investigate parameters regulating conjugation using an
Escherichia coli
laboratory strain that lacks plasmids or restriction enzyme modification systems as a recipient and also using patient isolates as donors and recipients. Because conjugation is tightly regulated, we performed a systematic analysis of the transfer of
Klebsiella pneumoniae
carbapenemase (
bla
KPC
)-encoding plasmids into multiple strains under different environmental conditions to investigate critical variables. We used four
bla
KPC
-carrying plasmids isolated from patient strains obtained from two hospitals: pKpQIL and pKPC-47e from the National Institutes of Health, and pKPC_UVA01 and pKPC_UVA02 from the University of Virginia. Plasmid transfer frequency differed substantially between different donor and recipient pairs, and the frequency was influenced by plasmid content, temperature, and substrate, in addition to donor and recipient strain. pKPC-47e was attenuated in conjugation efficiency across all conditions tested. Despite its presence in multiple clinical species, pKPC_UVA01 had lower conjugation efficiencies than pKpQIL into recipient strains. The conjugation frequency of these plasmids into
K. pneumoniae
and
E. coli
patient isolates ranged widely without a clear correlation with clinical epidemiological data. Our results highlight the importance of each variable examined in these controlled experiments. The
in vitro
models did not reliably predict plasmid mobilization observed in a patient population, indicating that further studies are needed to understand the most important variables affecting horizontal transfer
in vivo
.
Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii
Authors: García-Quintanilla Meritxell , Caro-Vega José M. , Pulido Marina R. , Moreno-Martínez Patricia , Pachón Jerónimo , McConnell Michael J. 
Published: June 2016

ABSTRACT

LpxC inhibitors have generally shown poor
in vitro
activity against
Acinetobacter baumannii
. We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant
A. baumannii
.
Pyrazinamide Is Active against Mycobacterium tuberculosis Cultures at Neutral pH and Low Temperature
Authors: den Hertog Alice L. , Menting Sandra , Pfeltz Richard , Warns Matthew , Siddiqi Salman H. , Anthony Richard M. 
Published: June 2016

ABSTRACT

For the past decades, an acidic pH has been used to render
Mycobacterium tuberculosis
susceptible to pyrazinamide for
in vitro
testing. Here, we show that at the standard breakpoint concentration and reduced culture temperatures, pyrazinamide (PZA) is active against tuberculosis (TB) at neutral pH. This finding should help unravel the mechanism of action of PZA and allow drug susceptibility testing (DST) methods to be optimized.
Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients
Authors: Kociolek Larry K. , Gerding Dale N. , Osmolski James R. , Patel Sameer J. , Snydman David R. , McDermott Laura A. , Hecht David W. 
Published: June 2016

ABSTRACT

The rising incidence of
Clostridium difficile
infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates.
C. difficile
was cultured from
tcdB
-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of
C. difficile
isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (
P
= 0.003); rifaximin, 1.6% and 6.7% (
P
= 0.11); clindamycin, 18.9% and 25.3% (
P
= 0.29); and moxifloxacin, 2.5% and 36% (
P
= <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (
P
= <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible
C. difficile
strains predominate in a cohort of children with CDI compared to adults.
Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections
Authors: Knippenberg Ben , Page-Sharp Madhu , Salman Sam , Clark Ben , Dyer John , Batty Kevin T. , Davis Timothy M. E. , Manning Laurens 
Published: June 2016

ABSTRACT

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (
r
> 0.95;
P
< 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.
Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome
bc
1
Inhibition Strategy for Malaria
Authors: Stickles Allison M. , Smilkstein Martin J. , Morrisey Joanne M. , Li Yuexin , Forquer Isaac P. , Kelly Jane X. , Pou Sovitj , Winter Rolf W. , Nilsen Aaron , Vaidya Akhil B. , Riscoe Michael K. 
Published: June 2016

ABSTRACT

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant
Plasmodium
parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome

bc
1

complex (cyt

bc
1

) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt

bc
1

: atovaquone (ATV) blocks the quinol oxidase (Q
o
) site of cyt

bc
1

, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Q
i
) site and retain full potency against ATV-resistant
Plasmodium falciparum
strains with Q
o
site mutations. Here, we provide the first
in vivo
comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using
P. yoelii
murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt

bc
1

is a valuable strategy for antimalarial combination therapy and that Q
i
site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Q
o
site inhibitor ATV.
Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy
Authors: Roger Claire , Wallis Steven C. , Muller Laurent , Saissi Gilbert , Lipman Jeffrey , Lefrant Jean-Yves , Roberts Jason A. 
Published: June 2016

ABSTRACT

The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h
−1
for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h
−1
for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (
C
max
)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.)
Chelation of Membrane-Bound Cations by Extracellular DNA Activates the Type VI Secretion System in Pseudomonas aeruginosa
Authors: Wilton Mike , Wong Megan J. Q. , Tang Le , Liang Xiaoye , Moore Richard , Parkins Michael D. , Lewenza Shawn , Dong Tao G. 
Published: June 2016

ABSTRACTPseudomonas aeruginosaemploys its type VI secretion system (T6SS) as a highly effective and tightly regulated weapon to deliver toxic molecules to target cells. T6SS-secreted proteins ofP. aeruginosacan be detected in the sputum of cystic fibrosis (CF) patients, who typically present a chronic and polymicrobial lung infection. However, the mechanism of T6SS activation in the CF lung is not fully understood. Here we demonstrate that extracellular DNA (eDNA), abundant within the CF airways, stimulates the dynamics of the H1-T6SS cluster apparatus inPseudomonas aeruginosaPAO1. Addition of Mg2+or DNase with eDNA abolished such activation, while treatment with EDTA mimicked the eDNA effect, suggesting that the eDNA-mediated effect is due to chelation of outer membrane-bound cations. DNA-activated H1-T6SS enablesP. aeruginosato nonselectively attack neighboring species regardless of whether or not it was provoked. Because of the importance of the T6SS in interspecies interactions and the prevalence of eDNA in the environments thatP. aeruginosainhabits, our report reveals an important adaptation strategy that likely contributes to the competitive fitness ofP. aeruginosain polymicrobial communities.
Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A
Authors: Cowardin Carrie A. , Jackman Brianna M. , Noor Zannatun , Burgess Stacey L. , Feig Andrew L. , Petri William A. 
Published: June 2016

ABSTRACTClostridium difficileis a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterizeC. difficileinfection (CDI) are primarily due to the Rho-glucosylating toxins A and B. These toxins cause epithelial cell death and induce robust inflammatory signaling by activating the transcription factor NF-κB, leading to chemokine and cytokine secretion. The toxins also activate the inflammasome complex, which leads to secretion of the pyrogenic cytokine IL-1β. In this study, we utilized glucosylation-deficient toxin A to show that activation of the inflammasome by this toxin is dependent on Rho glucosylation, confirming similar findings reported for toxin B. We also demonstrated that tissue destruction andin vivoinflammatory cytokine production are critically dependent on the enzymatic activity of toxin A, suggesting that inhibiting toxin glucosyltransferase activity may be effective in combating this refractory disease.
Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract
Authors: Dai Jin , Zhang Tianyuan , Wang Luying , Shao Lili , Zhu Cuiming , Zhang Yuyang , Failor Courtney , Schenken Robert , Baseman Joel , He Cheng , Zhong Guangming 
Published: June 2016

ABSTRACTChlamydiahas been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown thatChlamydia muridarumspreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenousC. muridarumcan spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressingC. muridarumstrain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. Theex vivoimaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro-orbital vein inoculation of theC. muridarumorganisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenousC. muridaruminoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract.