bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical Investigation of the Performance of a High Pressure Direct Injection (HPDI) Natural Gas Engine
Authors: Lee Won Geun , Montgomery David 
Published: December 2014

High Pressure Direct-Injection (HPDI) is a technology option for engines used in mobile equipment applications where use of LNG as a fuel is desired. Using the combination of a diesel pilot injection and direct gas injection, HPDI has the potential to deliver low emissions, excellent transient performance, high efficiency, and high gas substitution. When the HPDI program was initially undertaken, in order to aid in initial hardware design, 3-dimensional computational fluid dynamic modeling was conducted to understand the mixing and reaction processes in the combustion chamber of an HPDI engine. Gaining insight into qualitative trends of operation parameters and hardware configurations was a first critical step toward delivering a hardware set to demonstrate HPDI natural gas combustion system capabilities.
To model the combustion of multi-component fuel at arbitrary constituent ratios, a combustion model based on a detailed chemical kinetics approach was employed. Several published mechanisms and combinations of established mechanisms were tested by comparing results with existing fumigated dual fuel engine results. The result shows that some of combined mechanisms for n-heptane combustion and methane combustion are capable of adequately predicting combustion behavior in diesel-natural gas dual fuel combustion systems. One of the reduced n-heptane mechanisms (by Patel et al.) also matched dual fuel combustion results reasonably well.
This preliminary simulation study was conducted with typical trapped air conditions and fuel quantities matching the energy delivery for a 100 % load condition in existing DI diesel engines. A full 360-degree mesh at intake valve closing was constructed and a detailed geometry of the gas injector nozzle and sac area was modeled in locally refined grids using a Caterpillar proprietary CFD code that accepts industry standard mechanisms. The diesel pilot injection followed by gas injection and resulting combustion inside an HPDI engine was simulated from IVC through the compression and combustion strokes. The operating parameters — such as diesel pilot injection timing, pilot injection amount, and start of gas injection — were varied, and the effect on IMEP, NOx, CO and cylinder pressure were investigated. It was shown that the start of gas injection is the strongest parameter for control of combustion. Subsequent to the work discussed in this paper, the hardware configuration established as optimal during the modeling work was carried forward to the physical engine testing and was successful in delivering the performance and emissions goals without modification, demonstrating the accuracy and value of modern combustion modeling.
Impact of Very High Injection Pressure on Soot Emissions of Medium Speed Large Diesel Engines
Authors: Engelmayer Michael , Taucher Gert , Wimmer Andreas , Hirschl Gernot , Kammerdiener Thomas 
Published: December 2014

Measures exist to adjust tailpipe NOx emissions to assigned values, for example cooled exhaust gas recirculation (EGR) or a SCR catalyst in conjunction with urea. The situation is quite different with soot when use of a trap is not feasible for reasons of cost, space requirements and maintenance. Due to the highly complex soot formation and oxidation process, soot emissions can’t be targeted as easily as NOX. So how can soot be kept within the limits?
In principle, soot can be controlled by allocating sufficient oxygen and establishing good mixing conditions with vaporized fuel. The most effective measures target the injection system, e.g. increasing injection pressure, applying multiple injections, optimizing nozzle geometry.
To investigate the impact of very high injection pressure on soot, an advanced injection system with rail pressure capability up to 3000 bar and a Bosch injector was installed at the Large Engines Competence Center (LEC) in Graz. Full load and part load operating points at constant speed and in accordance with the propeller law were investigated at the test bed to quantify the impact of high injection pressure on soot emissions. Test runs were conducted with both SCR and EGR while varying injection timing and air-fuel ratios. Use of a statistical method, Design of Experiments (DOE), helped reduce the number of tests.
Optical investigations of the spray and combustion were conducted. The goal was to obtain soot concentration history traces with the two color method in order to better understand how soot originates and to be able to calibrate 3D CFD FIRE spray models for use with injection pressures of up to 3000 bar.
Very low soot emissions can be achieved using high pressure injection, even when EGR is applied. DOE results provide a clear picture of the relationships between the parameters and can be used to optimize set values for the whole speed and load range.
A reliable spray break up model can be used in further 3D CFD simulation to investigate how to reduce soot emissions.
In Vitro
Activity of Ceftazidime-Avibactam Combination in
In Vitro
Checkerboard Assays
Authors: Berkhout Johanna , Melchers Maria J. , van Mil Anita C. , Nichols Wright W. , Mouton Johan W. 
Published: December 2014

ABSTRACT

To evaluate the
in vitro
effects of the combination of ceftazidime and avibactam on the MICs of both compounds, checkerboard assays were performed for 81 clinical strains, including 55
Enterobacteriaceae
strains (32
Klebsiella pneumoniae
, 19
Escherichia coli
, 1
Citrobacter freundii
, and 3
Enterobacter cloacae
) and 26 strains of
Pseudomonas aeruginosa
, all with known resistance mechanisms such as extended-spectrum β-lactamases (ESBLs) and carbapenemases, phenotypically or molecularly determined. Phenotypically ceftazidime-resistant strains (
n
= 69) were analyzed in more detail. For the
Enterobacteriaceae
strains, a concentration-dependent effect of avibactam was found for most strains with a maximum effect of avibactam at a concentration of 4 mg/liter, which decreased all ceftazidime MICs to ≤4 mg/liter. Avibactam alone also showed antibacterial activity (the MIC
50
and MIC
90
being 8 and 16 mg/liter, respectively). For the ceftazidime-resistant
P. aeruginosa
strains, considerable inhibition of β-lactamases by avibactam was acquired at a concentration of 4 mg/liter, which decreased all ceftazidime MICs except one to ≤8 mg/liter (the CLSI and EUCAST susceptible breakpoint). Increasing the concentration of avibactam further decreased the MICs, resulting in a maximum effect for most strains at 8 to 16 mg/liter. In summary, for most strains, the tested addition of avibactam of 4 mg/liter restored the antibacterial activity of ceftazidime to a level comparable to that of wild-type strains, indicating full inhibition, and strains became susceptible according to the EUCAST and CLSI criteria. Based on these
in vitro
data, avibactam is a promising inhibitor of different β-lactamases, including ESBLs and carbapenemases.
Microbiome Changes in Healthy Volunteers Treated with GSK1322322, a Novel Antibiotic Targeting Bacterial Peptide Deformylase
Authors: Arat Seda , Spivak Aaron , Van Horn Stephanie , Thomas Elizabeth , Traini Christopher , Sathe Ganesh , Livi George P. , Ingraham Karen , Jones Lori , Aubart Kelly , Holmes David J. , Naderer Odin , Brown James R. 
Published: December 2014

ABSTRACT

GSK1322322 is a novel antibacterial agent under development, and it has known antibacterial activities against multidrug-resistant respiratory and skin pathogens through its inhibition of the bacterial peptide deformylase. Here, we used next-generation sequencing (NGS) of the bacterial 16S rRNA genes from stool samples collected from 61 healthy volunteers at the predosing and end-of-study time points to determine the effects of GSK1322322 on the gastrointestinal (GI) microbiota in a phase I, randomized, double-blind, and placebo-controlled study. GSK1322322 was administered either intravenously (i.v.) only or in an oral-i.v. combination in single- and repeat-dose-escalation infusions. Analysis of the 16S rRNA sequence data found no significant changes in the relative abundances of GI operational taxonomic units (OTUs) between the prestudy and end-of-study samples for either the placebo- or i.v.-only-treated subjects. However, oral-i.v. treatment resulted in significant decreases in some bacterial taxa, the
Firmicutes
and
Bacteroidales
, and increases in others, the
Betaproteobacteria
,
Gammaproteobacteria
, and
Bifidobacteriaceae
. Microbiome diversity plots clearly differentiated the end-of-study oral-i.v.-dosed samples from all others collected. The changes in genome function as inferred from species composition suggest an increase in bacterial transporter and xenobiotic metabolism pathways in these samples. A phylogenetic analysis of the peptide deformylase protein sequences collected from the published genomes of clinical isolates previously tested for GSK1322322
in vitro
susceptibility and GI bacterial reference genomes suggests that antibiotic target homology is one of several factors that influences the response of GI microbiota to this antibiotic. Our study shows that dosing regimen and target class are important factors when considering the impact of antibiotic usage on GI microbiota. (This clinical trial was registered at the GlaxoSmithKline Clinical Study Register under study identifier PDF 113376.)
Added Benefit of Raxibacumab to Antibiotic Treatment of Inhalational Anthrax
Authors: Migone Thi-Sau , Bolmer Sally , Zhong John , Corey Al , Vasconcelos Daphne , Buccellato Matthew , Meister Gabriel 
Published: December 2014

ABSTRACT

Although antibiotics treat bacteremia in inhalational anthrax, pathogenesis is mainly driven by bacterial exotoxins. Raxibacumab, an IgG1 monoclonal antibody, binds the protective antigen (PA) of
Bacillus anthracis
, thus blocking toxin effects and leading to improved survival in the rabbit and monkey models of inhalational anthrax. To assess raxibacumab's added benefit over levofloxacin (LVX) alone, rabbits surviving to 84 h after a challenge with 200 times the median (50%) lethal dose of
B. anthracis
spores were randomized to receive 3 daily intragastric LVX doses of 50 mg/kg of body weight, with the first LVX dose administered just prior to administration of a single intravenous dose of placebo or 40 mg/kg raxibacumab. The percentages of animals alive at 28 days following the last LVX dose were compared between the 2 treatment groups using a two-sided likelihood-ratio chi-square test. The 82% survival rate for the LVX-raxibacumab combination was higher than the 65% survival rate for LVX alone (
P
= 0.0874). There were nearly 2-fold fewer deaths for the combination (7 deaths;
n
= 39) than for LVX alone (13 deaths;
n
= 37), and the survival time was prolonged for the combination (
P
= 0.1016). Toxin-neutralizing-activity titers were similar for both treatment groups, suggesting that survivors in both groups were able to mount a toxin-neutralizing immune response. Microscopic findings considered consistent with anthrax were present in animals that died or became moribund on study in both treatment groups, and there were no anthrax-related findings in animals that survived. Overall, raxibacumab provided a meaningful benefit over antibiotic alone when administered late in the disease course.
Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2 Diabetes
Authors: Herrera Bruno S. , Hasturk Hatice , Kantarci Alpdogan , Freire Marcelo O. , Nguyen Olivia , Kansal Shevali , Van Dyke Thomas E. 
Published: December 2014

ABSTRACT

Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (
db
/
db
), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (
ERV1
), and a newly bred strain of
db
/
ERV1
mice, were used to determine the impact of RvE1 on the phagocytosis of
Porphyromonas gingivalis
in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled
P. gingivalis
, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the
in vivo
impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of
P. gingivalis
in WT animals but had no impact in
db
/
db
animals. In
ERV1
-transgenic and
ERV1
-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals.
In vivo
dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of
P. gingivalis
in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing
ERV1
.
Mechanisms of Protection against Clostridium difficile Infection by the Monoclonal Antitoxin Antibodies Actoxumab and Bezlotoxumab
Authors: Yang Zhiyong , Ramsey Jeremy , Hamza Therwa , Zhang Yongrong , Li Shan , Yfantis Harris G. , Lee Dong , Hernandez Lorraine D. , Seghezzi Wolfgang , Furneisen Jamie M. , Davis Nicole M. , Therien Alex G. , Feng Hanping 
Published: December 2014

ABSTRACT

Clostridium difficile
infection (CDI) represents the most prevalent cause of antibiotic-associated gastrointestinal infections in health care facilities in the developed world. Disease symptoms are caused by the two homologous exotoxins, TcdA and TcdB. Standard therapy for CDI involves administration of antibiotics that are associated with a high rate of disease recurrence, highlighting the need for novel treatment paradigms that target the toxins rather than the organism itself. A combination of human monoclonal antibodies, actoxumab and bezlotoxumab, directed against TcdA and TcdB, respectively, has been shown to decrease the rate of recurrence in patients treated with standard-of-care antibiotics. However, the exact mechanism of antibody-mediated protection is poorly understood. In this study, we show that the antitoxin antibodies are protective in multiple murine models of CDI, including systemic and local (gut) toxin challenge models, as well as primary and recurrent models of infection in mice. Systemically administered actoxumab-bezlotoxumab prevents both the damage to the gut wall and the inflammatory response, which are associated with
C. difficile
in these models, including in mice challenged with a strain of the hypervirulent ribotype 027. Furthermore, mutant antibodies (N297Q) that do not bind to Fcγ receptors provide a level of protection similar to that of wild-type antibodies, demonstrating that the mechanism of protection is through direct neutralization of the toxins and does not involve host effector functions. These data provide a mechanistic basis for the prevention of recurrent disease observed in CDI patients in clinical trials.
Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus
Authors: Kaakoush Nadeem O. , Deshpande Nandan P. , Man Si Ming , Burgos-Portugal Jose A. , Khattak Faisal A. , Raftery Mark J. , Wilkins Marc R. , Mitchell Hazel M. 
Published: December 2014

ABSTRACT

Pathogenic species within the genus
Campylobacter
are responsible for a considerable burden on global health.
Campylobacter concisus
is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on
Campylobacter
virulence mechanisms, little is known regarding the immunological profile of the host response to
Campylobacter
infection. In this study, we describe a comprehensive global profile of innate immune responses to
C. concisus
infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of
C. concisus
. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in
C. concisus
-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with
C. concisus
, which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by
C. concisus
.
The Copenhagen Standardised MRI protocol to assess the pubic symphysis and adductor regions of athletes: outline and intratester and intertester reliability
Authors: Branci Sonia , Thorborg Kristian , Bech Birthe Højlund , Boesen Mikael , Magnussen Erland , Court-Payen Michel , Nielsen Michael Bachmann , Hölmich Per 
Published: December 2014

BackgroundThere is currently no standardised MRI evaluation protocol for athletes who present with symptoms that may relate to the pubic symphysis, the pubic bones, and the adductor muscle insertions. We outline the protocol and reliability data.Material and methodsThree musculoskeletal radiologists developed an 11-element MRI evaluation protocol defined according to precise criteria and illustrated in a pictorial atlas. Eighty-six male athletes (soccer players and non-soccer players) underwent standardised 3 Tesla MRI of the pelvis. Two external musculoskeletal radiologists were trained to use the protocol and pictorial atlas during two sessions of 2–4 h each. Each radiologist rated all 86 MRI independently. One radiologist evaluated the scans once, the other twice 2 months apart. Cohen κ statistics were used to determine intraobserver and interobserver agreement.ResultsThe main findings were (1) substantial intraobserver (κ range 0.65–0.67) and moderate interobserver (κ range 0.45–0.52) agreement in rating pubic bone marrow oedema, (2) substantial to moderate intraobserver (κ range 0.49–0.72) and moderate-to-fair interobserver (κ range 0.21–0.52) agreement in rating most other MRI findings, (3) slight intraobserver and interobserver (κ range −0.06–0.05) agreement in rating adductor longus tendinopathy.ConclusionsThe Copenhagen Standardised MRI protocol demonstrated moderate-to-substantial reliability in rating bone marrow oedema, and varied from fair-to-substantial agreement for the majority of MRI features, but showed only slight agreement in rating adductor longus tendinopathy. This rigorous investigation also confirms that while MRI evaluation seems to provide reasonable reliability in rating pubic bone marrow oedema, the evaluation of adductor tendinopathy in a clinical and research setting needs further resolution by continued development and testing of MRI acquisition protocols.
Australian community pharmacy services: a survey of what people with chronic conditions and their carers use versus what they consider important
Authors: McMillan Sara S , Kelly Fiona , Sav Adem , King Michelle A , Whitty Jennifer A , Wheeler Amanda J 
Published: December 2014

ObjectiveTo explore the purpose/s for which people with chronic conditions and their carers use Australian community pharmacies, and compare this to what pharmacy services they consider important, from the perspectives of both consumers and pharmacists.DesignAn exploratory study involving a survey, which asked participants to indicate the pharmacy services they had ever used, and rate the importance of 22 pharmacy services to them, or the person they care for, or for their consumers if a pharmacist.SettingFour regions of Australia: Logan-Beaudesert and Mt Isa/North West region, Queensland, Northern Rivers, New South Wales, and the Greater Perth area, Western Australia.ParticipantsSurveys were undertaken with 602 consumers and 91 community pharmacists.ResultsCommunity pharmacy is predominantly used to obtain advice about medication and whether a doctor's visit is necessary, as well as for monitoring and screening services. Pharmacy services that were patient centric were important, such as individualised medication advice and respectful care, as well as tools or procedures to facilitate streamlined medication access. Less important services included adult vaccinations and health and wellness programmes. Carers identified services that assisted them with their specific role/s to be important. Overall, community pharmacists had a good understanding of the services that were important to people with chronic conditions and their carers.ConclusionsPeople with chronic conditions and their carers not only care about what services are delivered, but how they are delivered; they sought services that generally improved their access to medication and information, but in a way that was patient centred. Ultimately, pharmacists understood the importance of patient-centred care for people with chronic conditions and their carers, perhaps indicating a greater acceptance of integrating patient-centred care into their everyday practice.
Comparative outcomes of carotid artery stenting for asymptomatic and symptomatic carotid artery stenosis: a single-center prospective study
Authors: Mo Dapeng , Wang Bo , Ma Ning , Gao Feng , Miao Zhongrong 
Published: December 2014

BackgroundCarotid artery stenting (CAS) for symptomatic carotid artery stenosis (SCS) has been proved to be safe and effective in many randomized controlled trials, but the safety and efficacy of CAS for asymptomatic carotid artery stenosis (ACS) is not clear.ObjectiveTo prospectively compare the outcomes of CAS between patients with ACS and SCS.Methods402 consecutive patients, 233 with ACS and 169 with SCS, underwent CAS. The primary outcome was a composite of death, stroke or myocardial infarction at 30 days and during the follow-up period. Procedural success and complications such as hyperperfusion, sinus-cardiac reflex, gastrointestinal hemorrhage, myocardial infarction, acute thrombosis, and vagus nerve reflex were also compared between the ACS and SCS groups.ResultsCAS was successful in all patients. There were no significant differences in baseline characteristics of the patients (age, gender, hypertension, diabetes, smoking, alcohol consumption and dyslipidemia) and in 30-day or long-term follow-up outcomes between the ACS and SCS groups.ConclusionsPeriprocedural and long-term follow-up outcomes of CAS appear similar for ACS and SCS.