bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Irregular Frequency in Multi-Body Problem and Free-Surface Singularity Treatment
Authors: Liu Yujie , Falzarano Jeffrey M. 
Published: October 2016

Multibody operations are routinely performed in offshore activities. One classical example is the FLNG and LNGC side-by-side offloading case. To understand the phenomenon occurring inside the gap is of growing interest to the offshore industry. One important issue is the existence of the irregular frequency effect. The effect can be confused with the physical resonance. Thus it needs to be removed.
An extensive survey of the previous approaches to the irregular frequency problem has been undertaken. The matrix formulated in the boundary integral equations will become nearly singular for some frequencies. The existence of numerical round-off errors will make the matrix still solvable by a direct solver, however will result in unreasonably large values in some aspects of the solution, namely the irregular frequency effect.
The removal of the irregular effect is important especially for multi-body hydrodynamic analysis in identifying the physical resonances caused by the configuration of floaters. This paper will mainly discuss the lid method on the internal free surface. To reach a higher accuracy, the singularity resulting from the Green function needs special care. Each term in the wave Green function will be evaluated using the corresponding analysis methods. Specifically, an analytical integral method is proposed to treat the log singularity. Finally, results with and without irregular frequency removal will be shown to demonstrate the effectiveness of our proposed method. The validation cases include mini-boxbarge, boxbarge and cylindrical dock, which has apparent irregular frequency effect in their output results.
A Response Model for Vortex Induced Vibrations in Low KC Number Flows
Authors: Vedeld Knut , Sollund Håvar , Fyrileiv Olav , Nestegård Arne 
Published: October 2016

Vortex induced vibrations (VIV) are generally less critical in wave dominated flow conditions than in pure current flows. A steady state response needs time to build up and continuous variation in flow velocity generally reduces the vibration amplitudes. For low Keulegan-Carpenter (KC) flows in-line VIV is generally removed entirely, replaced by forced response at the wave frequency, while cross-flow vibration amplitudes are reduced. For large KC numbers, the wave induced flow behaves similarly to a current and the oscillatory nature of the flow no longer influences the VIV response as much.
Empirical models to predict the influence of waves in VIV design of offshore cylindrical structures are formulated in offshore design codes. For most flow regimes the models are sound and supported by a solid base of empirical test data. There are, however, exceptions — particularly for the low KC number regime, defined here as LKCR. For such flows the oscillating pressure differentials which cause vortex induced vibrations are no longer governed by traditional dimensionless parameters such as the reduced velocity, but instead the oscillating lift is governed by the ratio between the eigen-frequency of the structure and the wave frequency. Particularly, the frequency of the lift force is twice the wave frequency in regular waves. In irregular wave conditions there are necessarily also spectral peaks at both the actual wave frequency and at three times the wave frequency, but the governing spectral density is concentrated at two times the wave frequency.
The present study introduces a novel response model to conservatively assess cross-flow VIV in LKCR.
The Dynamic Behavior of Sandwich Plate With Layered Graded Metallic Honeycomb Cores
Authors: Wang Zhihua , Li Shiqiang , Wang Genwei , Lu Guoyun , Zhao Longmao 
Published: October 2016

Sandwich cellular structure, associated with more excellent mechanical properties and physical characteristic, such as, panel ductility and high core compressibility, is widely used in aerospace, transportation, military equipment and civil infrastructure. Due to the special compression properties of functional graded cores, the graded sandwich structure presented more excellent impact resistance than the ungraded sandwich.
This article presents the results of experimental, numerical investigation into the failure mode and dynamic plastic response of layered graded sandwich plate with layered honeycomb cores to air blast loading. The core arrangements (different core density) effects on the structure’s deformation behavior, energy absorption and impact resistance were mainly discussed. Three typical failure modes can be observed, that was, local deformation, global bending and penetration failure. Under specific loading conditions, the graded sandwich had more excellent impact resistant and energy absorption ratio, especially for the density-decreased core arrangement sandwich.
Population Pharmacokinetics and Target Attainment of Ertapenem in Plasma and Tissue Assessed via Microdialysis in Morbidly Obese Patients after Laparoscopic Visceral Surgery
Authors: Wittau Mathias , Paschke Stephan , Kurlbaum Max , Scheele Jan , Ly Neang S. , Hemper Evelyn , Kornmann Marko , Henne-Bruns Doris , Bulitta Jürgen B. 
Published: October 2016

ABSTRACT

Ertapenem provides broad-spectrum activity against many pathogens, and its use is relevant for the prophylaxis and treatment of infections in morbidly obese patients undergoing surgery. However, its pharmacokinetics and tissue penetration in these patients are not well defined. We assessed the population pharmacokinetics and target attainment for ertapenem in the plasma, subcutaneous tissue, and peritoneal fluid of morbidly obese patients. Six female patients (body mass index, 43.7 to 55.9 kg/m
2
) received 1,000 mg ertapenem as 15-min infusions at 0 and 26 h. On day 2, the unbound ertapenem concentrations in plasma, subcutaneous tissue, and peritoneal fluid were measured by microdialysis; total plasma concentrations were additionally quantified. The probability of attaining a target of an unbound ertapenem concentration above the MIC for at least 40% of the dosing interval was predicted via Monte Carlo simulations. The population pharmacokinetic model contained two disposition compartments and simultaneously described all concentrations. For unbound ertapenem, total clearance was 12.3 liters/h (coefficient of variation, 21.6% for between-patient variability) and the volume of distribution at steady state was 57.8 liters in patients with a 53-kg fat-free mass. The area under the concentration-time curve (AUC) for ertapenem was 49% lower in subcutaneous tissue and 25% lower in peritoneal fluid than the unbound AUC in plasma. Tissue penetration was rapid (equilibration half-life, <15 min) and was variable in subcutaneous tissue. Short-term ertapenem infusions (1,000 mg every 24 h) achieved robust (>90%) target attainment probabilities for MICs of up to 1 mg/liter in plasma, 0.25 to 0.5 mg/liter in subcutaneous tissue, and 0.5 mg/liter in peritoneal fluid. Ertapenem presents an attractive choice for many pathogens relevant to morbidly obese patients undergoing surgery. (This study has been registered at ClinicalTrials.gov under identifier NCT01407965.)
Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice
Authors: Yu Pei , Hu Yang , Liu Zhiqiang , Kawai Toshihisa , Taubman Martin A. , Li Wei , Han Xiaozhe 
Published: October 2016

ABSTRACTInterleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in the immune system balance by negatively regulating inflammatory responses. This study was conducted to determine the effect of local B10 cell induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitisin vivo. Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and the Toll-like receptor 9 (TLR9) agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 inductionin vitro. Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on day 0, followed by the injection of CD40L and CpG into the palatal gingiva on days 3, 6, and 9. All the mice were sacrificed, and samples were collected on day 14. CD40L and CpG significantly increased the level of IL-10 production by B cellsin vitro, although the frequencies of CD1dhiCD5+and IL-10-producing (IL-10+) CD45+cells were decreased. IL-10 was predominantly produced by the CD1dhiCD5+subpopulation of B cells.In vivo, both IL-10 mRNA expression and the number of IL-10+CD45+cells were significantly increased after gingival injection of CD40L and CpG. Periodontal bone loss was significantly decreased and the gingival expression of IL-1β, tumor necrosis factor alpha, and RANKL was significantly reduced. The number of multinucleated tartrate-resistant acid phosphatase-positive cells along the alveolar bone surface was significantly decreased after gingival injection of CD40L and CpG. This study indicates for the first time that the local induction of B10 cell activity could inhibit periodontal inflammation and bone loss.
Filamentous Bacteriophage Produced by Pseudomonas aeruginosa Alters the Inflammatory Response and Promotes Noninvasive InfectionIn Vivo
Authors: Secor Patrick R. , Michaels Lia A. , Smigiel Kate S. , Rohani Maryam G. , Jennings Laura K. , Hisert Katherine B. , Arrigoni Allison , Braun Kathleen R. , Birkland Timothy P. , Lai Ying , Hallstrand Teal S. , Bollyky Paul L. , Singh Pradeep K. , Parks William C. 
Published: October 2016

ABSTRACTPseudomonas aeruginosais an important opportunistic human pathogen that lives in biofilm-like cell aggregates at sites of chronic infection, such as those that occur in the lungs of patients with cystic fibrosis and nonhealing ulcers. During growth in a biofilm,P. aeruginosadramatically increases the production of filamentous Pf bacteriophage (Pf phage). Previous work indicated that whenin vivoPf phage production was inhibited,P. aeruginosawas less virulent. However, it is not clear how the production of abundant quantities of Pf phage similar to those produced by biofilms underin vitroconditions affects pathogenesis. Here, using a murine pneumonia model, we show that the production of biofilm-relevant amounts of Pf phage prevents the dissemination ofP. aeruginosafrom the lung. Furthermore, filamentous phage promoted bacterial adhesion to mucin and inhibited bacterial invasion of airway epithelial cultures, suggesting that Pf phage trapsP. aeruginosawithin the lung. Thein vivoproduction of Pf phage was also associated with reduced lung injury, reduced neutrophil recruitment, and lower cytokine levels. Additionally, when producing Pf phage,P. aeruginosawas less prone to phagocytosis by macrophages than bacteria not producing Pf phage. Collectively, these data suggest that filamentous Pf phage alters the progression of the inflammatory response and promotes phenotypes typically associated with chronic infection.
Novel MicroRNA Involved in Host Response to Avian Pathogenic Escherichia coli Identified by Deep Sequencing and Integration Analysis
Authors: Jia Xinzheng , Nie Qinghua , Zhang Xiquan , Nolan Lisa K. , Lamont Susan J. 
Published: October 2016

ABSTRACT

Avian pathogenic
Escherichia coli
(APEC) causes one of the most common bacterial diseases of poultry worldwide. Effective control methods are therefore desirable and will be facilitated by a better understanding of the host response to the pathogen. Currently, microRNAs (miRNAs) involved in host resistance to APEC are unknown. Here, we applied RNA sequencing to explore the changed miRNAs and deregulated genes in the spleen of three groups of broilers: nonchallenged (NC), APEC-challenged with mild pathology (CM), and APEC-challenged with severe pathology (CS). Twenty-seven differentially expressed miRNAs (fold change >1.5;
P
value <0.01) were identified, including 13 miRNAs between the NC and CM, 17 between the NC and CS, and 14 between the CM and CS groups. Through functional analysis of these miRNA targets, 12 immune-related biological processes were found to be significantly enriched. Based on combined analyses of differentially expressed miRNAs and mRNAs within each of the three groups, 43 miRNA-mRNA pairs displayed significantly negative correlations (
r
< −0.8). Notably, gga-miR-429 was greatly increased in the CS group compared to levels in both the CM and NC groups.
In vitro
, gga-miR-429 directly repressed luciferase reporter gene activity via binding to 3′ untranslated regions of TMEFF2, NTRK2, and SHISA2. Overexpression of gga-miR-429 in the HD11 macrophage cell line significantly inhibited TMEFF2 and SHISA2 expression, which are involved in the lipopolysaccharide-induced platelet-derived growth factor (PDGF) and Wnt signaling pathways. In summary, we provide the first report characterizing the miRNA changes during APEC infection, which may help to shed light on the roles of these recently identified genetic elements in the mechanisms of host resistance and susceptibility to APEC.
Entry of Botulinum Neurotoxin Subtypes A1 and A2 into Neurons
Authors: Kroken Abby R. , Blum Faith C. , Zuverink Madison , Barbieri Joseph T. 
Published: October 2016

ABSTRACT

Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans but also are common therapies for neurological diseases. BoNTs are dichain toxins, comprising an N-terminal catalytic domain (LC) disulfide bond linked to a C-terminal heavy chain (HC) which includes a translocation domain (H
N
) and a receptor binding domain (H
C
). Recently, the BoNT serotype A (BoNT/A) subtypes A1 and A2 were reported to possess similar potencies but different rates of cellular intoxication and pathology in a mouse model of botulism. The current study measured H
C
A1 and H
C
A2 entry into rat primary neurons and cultured Neuro2A cells. We found that there were two sequential steps during the association of BoNT/A with neurons. The initial step was ganglioside dependent, while the subsequent step involved association with synaptic vesicles. H
C
A1 and H
C
A2 entered the same population of synaptic vesicles and entered cells at similar rates. The primary difference was that H
C
A2 had a higher degree of receptor occupancy for cells and neurons than HcA1. Thus, H
C
A2 and H
C
A1 share receptors and entry pathway but differ in their affinity for receptor. The initial interaction of H
C
A1 and H
C
A2 with neurons may contribute to the unique pathologies of BoNT/A1 and BoNT/A2 in mouse models.
EssE Promotes Staphylococcus aureus ESS-Dependent Protein Secretion To Modify Host Immune Responses during Infection
Authors: Anderson Mark , Ohr Ryan Jay , Aly Khaled A. , Nocadello Salvatore , Kim Hwan K. , Schneewind Chloe E. , Schneewind Olaf , Missiakas Dominique 
Published: October 2016

ABSTRACT

Staphylococcus aureus
, an invasive pathogen of humans and animals, requires a specialized ESS pathway to secrete proteins (EsxA, EsxB, EsxC, and EsxD) during infection. Expression of
ess
genes is required for
S. aureus
establishment of persistent abscess lesions following bloodstream infection; however, the mechanisms whereby effectors of the ESS pathway implement their virulence strategies were heretofore not known. Here, we show that EssE forms a complex with other members of the ESS secretion pathway and its substrates, promoting the secretion of EsxA, EsxB, EsxC, EsxD, and EssD. During bloodstream infection of mice, the
S. aureus
essE
mutant displays defects in host cytokine responses, specifically in the production of interleukin-12 (IL-12) (p40/p70) and the suppression of RANTES (CCL5), activators of T
H
1 T cell responses and immune cell chemotaxis, respectively. Thus,
essE
-mediated secretion of protein effectors via the ESS pathway may enable
S. aureus
to manipulate host immune responses by modifying the production of cytokines.

IMPORTANCE
Staphylococcus aureus
and other firmicutes evolved a specialized ESS (
E
sxA/ESAT-6-like
s
ecretion
s
ystem) pathway for the secretion of small subsets of proteins lacking canonical signal peptides. The molecular mechanisms for ESS-dependent secretion and their functional purpose are still unknown. We demonstrate here that
S. aureus
EssE functions as a membrane assembly platform for elements of the secretion machinery and their substrates. Furthermore,
S. aureus
EssE-mediated secretion contributes to the production or the suppression of specific cytokines during host infection, thereby modifying immune responses toward this pathogen.
Functional Characterization of EscK (Orf4), a Sorting Platform Component of the Enteropathogenic Escherichia coli Injectisome
Authors: Soto Eduardo , Espinosa Norma , Díaz-Guerrero Miguel , Gaytán Meztlli O. , Puente José L. , González-Pedrajo Bertha 
Published: October 2016

ABSTRACT

The type III secretion system (T3SS) is a supramolecular machine used by many bacterial pathogens to translocate effector proteins directly into the eukaryotic host cell cytoplasm. Enteropathogenic
Escherichia coli
(EPEC) is an important cause of infantile diarrheal disease in underdeveloped countries. EPEC virulence relies on a T3SS encoded within a chromosomal pathogenicity island known as the locus of enterocyte effacement (LEE). In this work, we pursued the functional characterization of the LEE-encoded protein EscK (previously known as Orf4). We provide evidence indicating that EscK is crucial for efficient T3S and belongs to the SctK (OrgA/YscK/MxiK) protein family, whose members have been implicated in the formation of a sorting platform for secretion of T3S substrates. Bacterial fractionation studies showed that EscK localizes to the inner membrane independently of the presence of any other T3SS component. Combining yeast two-hybrid screening and pulldown assays, we identified an interaction between EscK and the C-ring/sorting platform component EscQ. Site-directed mutagenesis of conserved residues revealed amino acids that are critical for EscK function and for its interaction with EscQ. In addition, we found that T3S substrate overproduction is capable of compensating for the absence of EscK. Overall, our data suggest that EscK is a structural component of the EPEC T3SS sorting platform, playing a central role in the recruitment of T3S substrates for boosting the efficiency of the protein translocation process.

IMPORTANCE
The type III secretion system (T3SS) is an essential virulence determinant for enteropathogenic
Escherichia coli
(EPEC) colonization of intestinal epithelial cells. Multiple EPEC effector proteins are injected via the T3SS into enterocyte cells, leading to diarrheal disease. The T3SS is encoded within a genomic pathogenicity island termed the locus of enterocyte effacement (LEE). Here we unravel the function of EscK, a previously uncharacterized LEE-encoded protein. We show that EscK is central for T3SS biogenesis and function. EscK forms a protein complex with EscQ, the main component of the cytoplasmic sorting platform, serving as a docking site for T3S substrates. Our results provide a comprehensive functional analysis of an understudied component of T3SSs.
Aqueous outflow facility after phacoemulsification with or without goniosynechialysis in primary angle closure: a randomised controlled study
Authors: Rodrigues Ian A , Alaghband Pouya , Beltran Agullo Laura , Galvis Elizabeth , Jones Stephanie , Husain Rahat , Lim K Sheng 
Published: October 2016

BackgroundGoniosynechialysis (GSL) to remove peripheral anterior synechiae (PAS) alongside standard cataract surgery has potential theoretical advantages, Published randomised trials, however, have not shown conclusive functional benefits and aqueous outflow changes following GSL are unknown. This study aimed to compare electronic Shiøtz tonographic aqueous outflow facility (TOF) following phacoemulsification with or without GSL in patients with primary angle closure (PAC) and PAC glaucoma. Secondary outcomes were changes in intraocular pressure (IOP) and use of glaucoma medications.MethodsProspective randomised pilot study of 26 patients on glaucoma medication, with ≥90° PAS and significant lens opacity. Patients were randomised 1:1 to receive phacoemulsification with intraocular lens (IOL) implantation only (phaco) or phacoemulsification with IOL plus GSL (phaco-GSL).ResultsFourteen patients were randomised to phaco-GSL and 12 to phaco alone. TOF increased with phaco-GSL from 0.099±0.07 μL/min/mm Hg to 0.194±0.07, μL/min/mm Hg, p=0.0006, while the phaco group showed no significant change. IOP reduced in both groups, but reduced significantly more following phaco-GSL (46.0%) compared with phaco alone (27.6%, p=0.04). Medication use and extent of PAS only reduced with phaco-GSL, from 0.923±0.86 to 0.384±0.18 medications, p=0.0279, and from 249.2±83.4 to 110.8±53.9° PAS, 6 months postoperatively. No serious adverse events occurred in either group.ConclusionsEyes randomised to both surgical groups had similar and good outcomes at 6 months in this pilot study. However, only eyes undergoing GSL combined with standard phacoemulsification had significantly increased TOF, reduced glaucoma medication dependence and PAS postoperatively. GSL should therefore be considered in such patients.Trial registration number:NCT00719290, Results.
THE COST EFFECTIVENESS OF EXERCISE-BASED CARDIAC REHABILITATION: A SYSTEMATIC REVIEW
Authors: Edwards K , Jones N , Newton J , Foster C , Judge A , Jackson K , Arden NK , Pinedo-Villanueva R 
Published: October 2016

AimsEconomic evaluations provide a useful comparative approach for considering costs and consequences on patient outcomes, thus providing a foundation for effective policy and decision making.1 2 This descriptive review aims to better understand how economic evaluations of cardiac rehabilitation (CR) services are conducted to inform future research addressing the impact of a physical exercise component on cost-effectiveness.MethodsElectronic databases were searched for economic evaluations of exercise-based CR programs published in English between 2000 and 2014. The methodological quality of included economic evaluations was reviewed using criteria taken from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.3ResultsFifteen economic studies met the eligibility criteria but exhibited wide variability in study perspective, time horizon, setting, comparators and included costs, with significant heterogeneity for exercise dose between interventions. Ten evaluations were based on randomised controlled trials (RCTs) with time horizons between 6–24 months, but which largely produced weak or inconclusive results. Excluding two modelling studies, only three studies utilised longer time horizons (3.5–5 years), and findings suggest exercise-based CR leads to lowered costs, reduced rehospitalisation's and longer cumulative lifetime in the long-term.ConclusionsVariability in CR program delivery and exercise dose along with weak consistency between study perspective and included costs makes it difficult to compare cost and health outcomes between studies and accumulate evidence in support of a particular exercise regime. The dominance of RCTs with their extensive patient selectivity process and exclusion of comorbid patients questions whether cost-effectiveness findings would translate to a real-world setting. The use of longer time horizons would be more compatible with a chronic condition and allow the long-term effects of exercise-based CR to be evaluated.