bluuebunny/crossref_metadata_2025 huggingface dataset:
CHARACTERIZATION OF TAPIOCA STARCH PLASTICIZED BY 1-ETHYL-3-METHYLIMIDAZOLIUM ACETATE
Authors: Ismail Shajaratuldur , Mansor Nurlidia , Man Zakaria , Azizli Khairun Azizi
Published: August 2017

Starch is one of natural materials that been used for producing biodegradable materials. The starch-based materials are produced through a process known as gelatinization with the presence of plasticizer and elevated temperature. Properties of starch-based materials are lacking in terms of viscosity, water absorption, thermal and mechanical properties compare with synthetic materials. Researchers are involved in finding ways for improvement of starch-based materials properties and one of that is introducing new plasticizer. 1-ethyl-3-methylimidazolium acetate, [Emim][OAc] is an ionic liquid that used as plasticizer to produce thermoplastic starch. Starch plasticized by [Emim][OAc] were prepared with different total plasticizer contents (50%,70%) and [Emim][OAc]/water ratio (1:6,1:4,2:3 wt%). The thermoplastic starches were characterized in terms of morphology, crystalline structure and thermal degradation. The results showed that 70% of total plasticizer contents were mixed well during gelatinization process. [Emim][OAc] contributed to granule disruption as shown by SEM. Based on the XRD analysis, it was shown that thermoplastic starch at 70% total plasticizer contents and 1:4 wt% ratio of [Emim][OAc]/water, caused disruption of the A-type crystalline structure, generated VH-type crystalline structure and thus increased the mobility of the amorphous starch. The presence of [Emim][OAc] promotes the thermal degradation of starch molecules as described by TGA. Therefore, plasticizer contents and [Emim][OAc]/water ratio are vital parameters that influences the properties of thermoplastic starch.
BIS(BIPYRIDYL)-RU(II)-1-BENZOYL-3-(PYRIDINE-2-YL)-1H-PYRAZOLE AS POTENTIAL PHOTOSENSITISER: EXPERIMENTAL AND DENSITY FUNCTIONAL THEORY STUDY
Authors: Mark-Lee Wun-Fui , Rusydi Febdian , Minggu Lorna Jeffery , Kubo Takashi , Kassim Mohammad
Published: August 2017

Ru(II) complexes, [Ru(bpy)2(m-R-L)](PF6)2 where bpy = 2,2’-bipyridyl and  m-R-L= 1-(meta-R)-benzoyl-3-(pyridine-2-yl)-1H-pyrazole derivatives (R = H, CH3 and Cl) abbreviated as RuL, Ru(m-CH3-L) and Ru(m-Cl-L) complexes, respectively, were synthesized and characterized with spectroscopic techniques namely, infrared, UV-Vis and nuclear magnetic resonance (NMR), photoluminescence and mass spectroscopy. Density functional theory (DFT) and time-dependent (TD) DFT calculations were carried out to study the structural and electronic features of the molecules. These Ru(II) complexes exhibit photo-electronic properties required for a photosensitiser in a TiO2-catalysed photoelectrochemical (PEC) cell. In-depth understanding of the R-L fragment functionality is important to tune the photo-electronic properties of the Ru(II) complex. The highest-occupied molecular orbital (HOMO) is mainly localized at the Ru(II) centre, while the LUMO is dominantly spread across the R-L ligand. The Ru(II) complexes showed favourable metal-to-ligand charge transfer (MLCT) energy levels, which are comparably higher than the conduction band of TiO2 to facilitate electron injection process. Among the Ru(II) complexes, Ru(m-Cl-L) comparatively possesses the highest photoluminescence quantum yield and has the potential to be applied as photosensitiser in PEC systems.
Influence of lung volume on the interaction between cardiac output and cerebrovascular regulation during extreme apnoea
Authors: Stembridge Mike , Hoiland Ryan L. , Bain Anthony R. , Barak Otto F. , Drvis Ivan , MacLeod David B. , MacLeod Douglas M. , Madden Dennis , Batinic Tonci , O'Donoghue Peter , Shave Rob , Dujic Zeljko , Ainslie Philip N.
Published: August 2017

New Findings

What is the central question of this study?

Does the reduction in cardiac output observed during extreme voluntary apnoea, secondary to high lung volume, result in a reduction in cerebral blood flow, perfusion pressure and oxygen delivery in a group of elite free divers?

What is the main finding and its importance?

High lung volumes reduce cardiac output and ventricular filling during extreme apnoea, but changes in cerebral blood flow are observed only transiently during the early stages of apnoea. This reveals that whilst cardiac output is important in regulating cerebral haemodynamics, the role of mean arterial pressure in restoring cerebral perfusion pressure is of greater significance to the regulation of cerebral blood flow.

We investigated the role of lung volume‐induced changes in cardiac output () on cerebrovascular regulation during prolonged apnoea. Fifteen elite apnoea divers (one female; 185 ± 7 cm, 82 ± 12 kg, 29 ± 7 years old) attended the laboratory on two separate occasions and completed maximal breath‐holds at total lung capacity (TLC) and functional residual capacity (FRC) to elicit disparate cardiovascular responses. Mean arterial pressure (MAP), internal jugular venous pressure and arterial blood gases were measured via cannulation. Global cerebral blood flow was quantified by ultrasound and cardiac output was quantified by via photoplethysmography. At FRC, stroke volume and did not change from baseline (P > 0.05). In contrast, during the TLC trial stroke volume and were decreased until 80 and 40% of apnoea, respectively (P < 0.05). During the TLC trial, global cerebral blood flow was significantly lower at 20%, but subsequently increased so that cerebral oxygen delivery was comparable to that during the FRC trial. Internal jugular venous pressure was significantly higher throughout the TLC trial in comparison to FRC. The MAP increased progressively in both trials but to a greater extent at TLC, resulting in a comparable cerebral perfusion pressure between trials by the end of apnoea. In summary, although lung volume has a profound effect on during prolonged breath‐holding, these changes do not translate to the cerebrovasculature owing to the greater sensitivity of cerebral blood flow to arterial blood gases and MAP; regulatory mechanisms that facilitate the maintenance of cerebral oxygen delivery.
Propagation of Input Uncertainty in Presence of Model-Form Uncertainty: A Multifidelity Approach for Computational Fluid Dynamics Applications
Authors: Wang Jian-Xun , Roy Christopher J. , Xiao Heng
Published: August 2017

Proper quantification and propagation of uncertainties in computational simulations are of critical importance. This issue is especially challenging for computational fluid dynamics (CFD) applications. A particular obstacle for uncertainty quantifications in CFD problems is the large model discrepancies associated with the CFD models used for uncertainty propagation. Neglecting or improperly representing the model discrepancies leads to inaccurate and distorted uncertainty distribution for the quantities of interest (QoI). High-fidelity models, being accurate yet expensive, can accommodate only a small ensemble of simulations and thus lead to large interpolation errors and/or sampling errors; low-fidelity models can propagate a large ensemble, but can introduce large modeling errors. In this work, we propose a multimodel strategy to account for the influences of model discrepancies in uncertainty propagation and to reduce their impact on the predictions. Specifically, we take advantage of CFD models of multiple fidelities to estimate the model discrepancies associated with the lower-fidelity model in the parameter space. A Gaussian process (GP) is adopted to construct the model discrepancy function, and a Bayesian approach is used to infer the discrepancies and corresponding uncertainties in the regions of the parameter space where the high-fidelity simulations are not performed. Several examples of relevance to CFD applications are performed to demonstrate the merits of the proposed strategy. Simulation results suggest that, by combining low- and high-fidelity models, the proposed approach produces better results than what either model can achieve individually.
Gas Turbine Compressor Fouling and Washing in Power and Aerospace Propulsion
Authors: Igie Uyioghosa
Published: August 2017

This paper presents a well-researched subject area within academia, with a high degree of application in the industry. Compressor fouling effect is one of the commonest degradations associated with gas turbine operations. The aim of this review is to broadly communicate some of the current knowledge while identifying some gaps in understanding, in an effort to present some industry/operational interest for academic research. Likewise, highlight some studies from academia that present the current state of research, with their corresponding methods (experimental, numerical, actual operations, and analytical methods). The merits and limitations of the individual method and their approaches are discussed, thereby providing industry practitioners with a view to appreciating academic research outputs. The review shows opportunities for improving compressor washing effectiveness through computational fluid dynamics (CFD). This is presented in the form of addressing the factors influencing compressor washing efficiency. Pertinent questions from academic research and operational experiences are posed, on the basis of this review.
Optimal Experimental Design Using a Consistent Bayesian Approach
Authors: Walsh Scott N. , Wildey Tim M. , Jakeman John D.
Published: August 2017

We consider the utilization of a computational model to guide the optimal acquisition of experimental data to inform the stochastic description of model input parameters. Our formulation is based on the recently developed consistent Bayesian approach for solving stochastic inverse problems, which seeks a posterior probability density that is consistent with the model and the data in the sense that the push-forward of the posterior (through the computational model) matches the observed density on the observations almost everywhere. Given a set of potential observations, our optimal experimental design (OED) seeks the observation, or set of observations, that maximizes the expected information gain from the prior probability density on the model parameters. We discuss the characterization of the space of observed densities and a computationally efficient approach for rescaling observed densities to satisfy the fundamental assumptions of the consistent Bayesian approach. Numerical results are presented to compare our approach with existing OED methodologies using the classical/statistical Bayesian approach and to demonstrate our OED on a set of representative partial differential equations (PDE)-based models.
Stochastic Bifurcations of a Nonlinear Acousto-Elastic System
Authors: Dheelibun Remigius W. , Sarkar Sunetra
Published: August 2017

The nonlinear stochastic behavior of a nonconservative acousto-elastic system is in focus in the present work. The deterministic acousto-elastic system consists of a spinning disk in a compressible fluid filled enclosure. The nonlinear rotating plate dynamics is coupled with the linear acoustic oscillations of the surrounding fluid, and the coupled field equations are discretized and solved at various rotation speeds. The deterministic system reveals the presence of a supercritical Hopf bifurcation when a specific coupled mode undergoes a flutter instability at a particular rotation speed. The effect of randomness associated with the damping parameters are investigated and quantified on the coupled dynamics and the stochastic bifurcation behavior is studied. The quantification of the parametric randomness has been undertaken by means of a spectral projection based polynomial chaos expansion (PCE) technique. From the marginal probability density functions (PDFs), it is observed that the stochastic system exhibits stochastic phenomenological bifurcations (P-bifurcation). The study provides insights into the behavior of the stochastic system during its P-bifurcation with reference to the deterministic Hopf bifurcation.
Dynamics Model of 4-SPS/CU Parallel Mechanism With Spherical Clearance Joint and Flexible Moving Platform
Authors: Wang Gengxiang , Liu Hongzhao
Published: August 2017

Effects of flexible body and clearance spherical joint on the dynamic performance of 4-SPS/CU parallel mechanism are analyzed. The flexible moving platform is treated as thin plate based on absolute nodal coordinate formulation (ANCF). In order to formulate the parallel mechanism's constraint equations between the flexible body and the rigid body, the tangent frame is introduced to define the joint coordinate. One of the spherical joints between moving platform and kinematic chains is introduced into clearance. The normal and tangential contact forces are calculated based on Flores contact force model and modified Coulomb friction model. The dynamics model of parallel mechanism with clearance spherical joint and flexible moving platform is formulated based on equation of motion. Simulations show that the dynamic performance of parallel mechanism is not sensitive to the flexible body because of the inherent property of moving platform; however, when the clearance spherical joint is considered into the parallel mechanism with flexible body, the flexible moving platform exhibits cushioning effect to absorb the energy caused by clearance joint.
Development and Evaluation of Flame-Assisted Dual Velocity Nanoparticle Coating System
Authors: Rukosuyev Maxym V. , Ali Baqar Syed , Jun Martin B. G.
Published: August 2017

The importance of coatings in modern science and industry is great, and the system presented in this manuscript attempts to provide a method of creating high quality nanoparticle coatings with in situ sintering of nanoparticles. Dual regime nozzle creates close to optimum conditions for particle delivery and deposition and the addition of in situ thermally assisted coating makes it more productive. Preliminary results show systems uniform coating and in situ sintering capability.
Enhanced Bonding by Applied Current in Cu-to-Cu Joints Fabricated Using 20 μm Cu Microbumps
Authors: Woo Ma Sung , Shin Chanho , Kim Young-Ho
Published: August 2017

The effect of applied current in enhancing bonding was studied in Cu-to-Cu direct bonding using Cu microbumps. A daisy-chain structure of electroplated Cu microbumps (20 μm × 20 μm) was fabricated on Si wafer. Cu-to-Cu bonding was performed in ambient atmosphere at 200–300 °C for 10 min under 260 MPa, during which direct current of 0–10 A (2.5 × 106 A/cm2) was applied. With increasing applied current, the contact resistance decreased and the shear strength in the Cu-to-Cu joints increased. The enhanced bonding imparted by the application of current was ascribed to Joule heating and electromigration effects. Subsequently, the joint temperature was calibrated to isolate the electromigration effects for study. In Cu-to-Cu joints joined at the same adjusted temperature, increasing the current caused unbonded regions to decrease and regions of cohesive failure to increase. The enhanced diffusion across the Cu/Cu interfaces under the applied current was the main mechanism whereby the quality of the Cu-to-Cu joints was improved.
Enhanced recrystallization and dopant activation of P+ ion-implanted super-thin Ge layers by RF hydrogen plasma treatment
Authors: Nazarov Alexei N. , Yukhymchuk Volodymyr O. , Gomeniuk Yurii V. , Kryvyi Sergiy B. , Okholin Pavel N. , Lytvyn Petro M. , Kladko Vasyl P. , Lysenko Volodymyr S. , Glotov Volodymyr I. , Golentus Illya E. , Napolitani Enrico , Duffy Ray
Published: August 2017

Radio-frequency (RF) hydrogen plasma treatment, thermal annealing in a furnace, and rapid thermal annealing of high-dose P+ ion implanted p-type Ge layers have been studied by Raman scattering spectroscopy, atomic force microscopy, secondary ion mass spectrometry, electrochemical capacitance–voltage profiling, four-point probes method, and x-ray reflectometry. It was shown that low-temperature RF plasma treatment at temperature about 200 °C resulted in full recrystallization of amorphous Ge layer implanted by P+ ions and activation of implanted impurity up to 6.5 × 1019 cm−3 with a maximum concentration at the depth of about 20 nm. Rapid thermal annealing (15 s) and thermal annealing (10 min) in nitrogen ambient required considerably higher temperatures for the recrystallization and activation processes that resulted in diffusion of implanted impurity inside the Ge bulk. It was demonstrated that RF plasma treatment from the samples with front (implanted) side resulted in considerable stronger effects of recrystallization and activation as compared with the same treatment from the back (unimplanted) side. The experiment shows that nonthermal processes play an important role in enhanced recrystallization and dopant activation during the RF plasma treatment. Mechanisms of enhanced modification of the subsurface implanted Ge layer under plasma treatment are analyzed.
The energy based characteristics of sperm whale clicks using the Hilbert Huang transform analysis method
Authors: Lin Chin-Feng , Chung Yao-Ching , Zhu Jin-De , Chang Shun-Hsyung , Wen Chan-Chuan , Parinov Ivan A. , Shevtsov S. N.
Published: August 2017

In this paper, a unique analysis method for sperm whale clicks based on Hilbert-Huang transform (HHT) is proposed. Four sperm whale click samples with durations of 10 ms (defined as click I), and four sperm whale click samples with durations of 5 ms (defined as click II) were illustrated. These click samples were recorded in the Mediterranean Sea by Centro Interdisciplinare di Bioacusticae Ricerche Ambientali, Università degli Studi di Pavia. The empirical mode decomposition method was used to decompose click I samples into seven intrinsic mode functions (IMFs) and one residue function (RF), and click II samples were decomposed into six IMFs and one RF. The average energy distributions of multiple IMFs and the single RF domain for click I and click II samples were explored using the HHT analysis method. The average energy-frequency representations were also investigated for the same click I and click II samples. The analysis results show that the energy-frequency characteristics of sperm whale clicks can be extracted and understood by applying several IMFs and one RF signal with a high-resolution analysis.
Caspofungin-Mediated Growth Inhibition and Paradoxical Growth in Aspergillus fumigatus Involve Fungicidal Hyphal Tip Lysis Coupled with Regenerative Intrahyphal Growth and Dynamic Changes in β-1,3-Glucan Synthase Localization
Authors: Moreno-Velásquez Sergio D. , Seidel Constanze , Juvvadi Praveen R. , Steinbach William J. , Read Nick D.
Published: August 2017

Caspofungin targets cell wall β-1,3-glucan synthesis and is the international consensus guideline-recommended salvage therapy for invasive aspergillosis. Although caspofungin is inhibitory at low concentrations, it exhibits a paradoxical effect (reversal of growth inhibition) at high concentrations by an undetermined mechanism. Treatment with caspofungin at either the growth-inhibitory concentration (0.5 μg/ml) or paradoxical growth-inducing concentration (4 μg/ml) for 24 h caused similar abnormalities, including wider, hyperbranched hyphae, increased septation, and repeated hyphal tip lysis, followed by regenerative intrahyphal growth. By 48 h, only hyphae at the colony periphery treated with the high caspofungin concentration displayed paradoxical growth. A similar high concentration of caspofungin also induced the paradoxical growth ofAspergillus fumigatusduring human A549 alveolar cell invasion. Localization of the β-1,3-glucan synthase complex (Fks1 and Rho1) revealed significant differences between cells exposed to the growth-inhibitory and paradoxical growth-inducing concentrations of caspofungin. At both concentrations, Fks1 initially mislocalized from the hyphal tips to vacuoles. However, only continuous exposure to 4 μg/ml of caspofungin for 48 h led to recovery of the normal hyphal morphology with renewed localization of Fks1 to hyphal tips. Rho1 remained at the hyphal tip after treatment with both caspofungin concentrations but was required for paradoxical growth. Farnesol blocked paradoxical growth and relocalized Fks1 and Rho1 to vacuoles. Our results highlight the importance of regenerative intrahyphal growth as a rapid adaptation to the fungicidal lytic effects of caspofungin on hyphal tips and the dynamic localization of Fks1 as part of the mechanism for the caspofungin-mediated paradoxical response inA. fumigatus.
Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae
Authors: Cojutti Piergiorgio , Sartor Assunta , Righi Elda , Scarparo Claudio , Bassetti Matteo , Pea Federico
Published: August 2017

We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Klebsiella pneumoniae
(KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations (
C
ss
) of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T
>1×MIC
, 100% T
>2×MIC
, 100% T
>3×MIC
, and 100% T
>4×MIC
, where “T
>MIC
” represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 (
n
= 169). Ninety-seven meropenem
C
ss
were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T
>1×MIC
against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.
A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries
Authors: Arias Cesar A. , Reyes Jinnethe , Carvajal Lina Paola , Rincon Sandra , Diaz Lorena , Panesso Diana , Ibarra Gabriel , Rios Rafael , Munita Jose M. , Salles Mauro J. , Alvarez-Moreno Carlos , Labarca Jaime , Garcia Coralith , Luna Carlos M. , Mejia-Villatoro Carlos , Zurita Jeannete , Guzman-Blanco Manuel , Rodriguez-Noriega Eduardo , Narechania Apurva , Rojas Laura J. , Planet Paul J. , Weinstock George M. , Gotuzzo Eduardo , Seas Carlos
Published: August 2017

Staphylococcus aureus
is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant
S. aureus
(MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185
S. aureus
) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette
mec
[SCC
mec
] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCC
mec
IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.
In Vitro
Evaluation of Biofilm Dispersal as a Therapeutic Strategy To Restore Antimicrobial Efficacy
Authors: Roizman Dan , Vidaillac Celine , Givskov Michael , Yang Liang
Published: August 2017

As a proof-of-concept study, the direct impact of biofilm dispersal on the
in vitro
efficacy of imipenem and tobramycin was evaluated against 3-day-old biofilms of
Pseudomonas aeruginosa
. Arabinose induction of biofilm dispersal via activation of the phosphodiesterase YhjH in the
P. aeruginosa
engineered strain PAO1/p

BAD

-
yhjH
resulted in increased antimicrobial efficacy and synergy of the imipenem-tobramycin combination. These results support the use of biofilm dispersal to enhance antimicrobial efficacy in the treatment of biofilm-associated infections, representing a promising therapeutic strategy.
Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections
Authors: Liu Dan , Gan Zhen-Shun , Ma Wan , Xiong Hai-Tao , Li Yun-Qing , Wang Yi-Zhen , Du Hua-Hua
Published: August 2017

Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and an infection threat and orchestrate a series of host-protective responses. Several studies have investigated the antimicrobial role of hepcidin, but the results have been controversial. Here, we aimed to examine the role of hepcidin in bacterial adherence and invasion
in vitro
. We found that porcine hepcidin could decrease the amount of the extracellular pathogen enterotoxigenic
Escherichia coli
(ETEC) K88 that adhered to cells because it caused the aggregation of the bacteria. However, addition of hepcidin to macrophages infected with the intracellular pathogen
Salmonella enterica
serovar Typhimurium enhanced the intracellular growth of the pathogen through the degradation of ferroportin, an iron export protein, and then the sequestration of intracellular iron. Intracellular iron was unavailable by use of the iron chelator deferiprone (DFO), which reduced intracellular bacterial growth. These results demonstrate that hepcidin exhibits different functions in extracellular and intracellular bacterial infections, which suggests that different defense strategies should be taken to prevent bacterial infection.
Stability of Proteins Out of Service: the GapB Case of Bacillus subtilis
Authors: Gerth Ulf , Krieger Eleonora , Zühlke Daniela , Reder Alexander , Völker Uwe , Hecker Michael
Published: August 2017

Bacillus subtilis
possesses two glyceraldehyde-3-phosphate dehydrogenases with opposite roles, the glycolytic NAD-dependent GapA and the NADP-dependent GapB enzyme, which is exclusively required during gluconeogenesis but not active under conditions promoting glycolysis. We propose that proteins that are no longer needed will be recognized and proteolyzed by Clp proteases and thereby recycled. To test this postulation, we analyzed the stability of the glycolytic enzyme GapA and the gluconeogenetic enzyme GapB in the presence and absence of glucose. It turned out that GapA remained rather stable under both glycolytic and gluconeogenetic conditions. In contrast, the gluconeogenetic enzyme GapB was degraded after a shift from malate to glucose (i.e., from gluconeogenesis to glycolysis), displaying an estimated half-life of approximately 3 h. Comparative
in vivo
pulse-chase labeling and immunoprecipitation experiments of the wild-type strain and isogenic mutants identified the ATP-dependent ClpCP protease as the enzyme responsible for the degradation of GapB. However, arginine protein phosphorylation, which was recently described as a general tagging mechanism for protein degradation, did not seem to play a role in GapB proteolysis, because GapB was also degraded in a
mcsB
mutant, lacking arginine kinase, in the same manner as in the wild type.

IMPORTANCE
GapB, the NADP-dependent glyceraldehyde-3-phosphosphate dehydrogenase, is essential for
B. subtilis
under gluconeogenetic conditions. However, after a shift to glycolytic conditions, GapB loses its physiological function within the cell and becomes susceptible to degradation, in contrast to GapA, the glycolytic NAD-dependent glyceraldehyde-3-phosphate dehydrogenase, which remains stable under glycolytic and gluconeogenetic conditions. Subsequently, GapB is proteolyzed in a ClpCP-dependent manner. According to our data, the arginine kinase McsB is not involved as adaptor protein in this process. ClpCP appears to be in charge in the removal of inoperable enzymes in
B. subtilis
, which is a strictly regulated process in which the precise recognition mechanism(s) remains to be identified.
Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens
Authors: Furniss R. Christopher D. , Clements Abigail
Published: August 2017

Attaching and effacing (AE) pathogens colonize the gut mucosa using a type three secretion system (T3SS) and a suite of effector proteins. The locus of enterocyte effacement (LEE) is the defining genetic feature of the AE pathogens, encoding the T3SS and the core effector proteins necessary for pathogenesis. Extensive research has revealed a complex regulatory network that senses and responds to a myriad of host- and microbiota-derived signals in the infected gut to control transcription of the LEE. These signals include microbiota-liberated sugars and metabolites in the gut lumen, molecular oxygen at the gut epithelium, and host hormones. Recent research has revealed that AE pathogens also recognize physical signals, such as attachment to the epithelium, and that the act of effector translocation remodels gene expression in infecting bacteria. In this review, we summarize our knowledge to date and present an integrated view of how chemical, geographical, and physical cues regulate the virulence program of AE pathogens during infection.
Comprehensive Arrayed Transposon Mutant Library of Klebsiella pneumoniae Outbreak Strain KPNIH1
Authors: Ramage Beth , Erolin Roxanne , Held Kiara , Gasper Joe , Weiss Eli , Brittnacher Mitch , Gallagher Larry , Manoil Colin
Published: August 2017

Klebsiella pneumoniae
and other carbapenem-resistant members of the family
Enterobacteriaceae
are a major cause of hospital-acquired infections, yet the basis of their success as nosocomial pathogens is poorly understood. To help provide a foundation for genetic analysis of
K. pneumoniae
, we created an arrayed, sequence-defined transposon mutant library of an isolate from the 2011 outbreak of infections at the U.S. National Institutes of Health Clinical Center. The library is made up of 12,000 individually arrayed mutants of a carbapenemase deletion parent strain and provides coverage of 85% of the predicted genes. The library includes an average of 2.5 mutants per gene, with most insertion locations identified and confirmed in two independent rounds of Sanger sequencing. On the basis of an independent transposon sequencing assay, about half of the genes lacking representatives in this “two-allele” library are essential for growth on nutrient agar. To validate the use of the library for phenotyping, we screened candidate mutants for increased antibiotic sensitivity by using custom phenotypic microarray plates. This screening identified several mutations increasing sensitivity to β-lactams (in
acrB1
,
mcrB
,
ompR
,
phoP1
, and
slt1
) and found that two-component regulator
cpxAR
mutations increased multiple sensitivities (to an aminoglycoside, a fluoroquinolone, and several β-lactams). Strains making up the two-allele mutant library are available through a web-based request mechanism.

IMPORTANCE
K. pneumoniae
and other carbapenem-resistant members of the family
Enterobacteriaceae
are recognized as a top public health threat by the Centers for Disease Control and Prevention. The analysis of these major nosocomial pathogens has been limited by the experimental resources available for studying them. The work presented here describes a sequence-defined mutant library of a
K. pneumoniae
strain (KPNIH1) that represents an attractive model for studies of this pathogen because it is a recent isolate of the major sequence type that causes infection, the epidemiology of the outbreak it caused is well characterized, and an annotated genome sequence is available. The ready availability of defined mutants deficient in nearly all of the nonessential genes of the model strain should facilitate the genetic dissection of complex traits like pathogenesis and antibiotic resistance.
Conformational Changes That Coordinate the Activity of BamA and BamD Allowing β-Barrel Assembly
Authors: McCabe Anne L. , Ricci Dante , Adetunji Modupe , Silhavy Thomas J.
Published: August 2017

Most integral outer membrane proteins (OMPs) of Gram-negative bacteria, such as
Escherichia coli
, assume a β-barrel structure. The β-barrel assembly machine (Bam), a five-member complex composed of β-barrel OMP BamA and four associated lipoproteins, BamB, BamC, BamD, and BamE, folds and inserts OMPs into the outer membrane. The two essential proteins BamA and BamD interact to stabilize two subcomplexes, BamAB and BamCDE, and genetic and structural evidence suggests that interactions between BamA and BamD occur via an electrostatic interaction between a conserved aspartate residue in a periplasmic domain of BamA and a conserved arginine in BamD. In this work, we characterize charge-change mutations at these key BamA and BamD residues and nearby charged residues in BamA with respect to OMP assembly and Bam complex stability. We show that Bam complex stability does not correlate with function, that BamA and BamD must adopt at least two active conformational states during OMP assembly, and that these charged residues are not required for function. Rather, these charged residues are important for coordinating the activities of BamA and BamD to allow efficient OMP assembly. We present a model of OMP assembly wherein recognition and binding of unfolded OMP substrate by BamA and BamD induce a signaling interaction between the two proteins, causing conformational changes necessary for the assembly reaction to proceed. By analogy to signal sequence recognition by SecYEG, we believe these BamA-BamD interactions ensure that both substrate and complex are competent for OMP assembly before the assembly reaction commences.

IMPORTANCE
Conformational changes in the proteins of the β-barrel assembly machine (Bam complex) are associated with the folding and assembly of outer membrane proteins (OMPs) in Gram-negative bacteria. We show that electrostatic interactions between the two essential proteins BamA and BamD coordinate conformational changes upon binding of unfolded substrate that allow the assembly reaction to proceed. Mutations affecting this interaction are lethal not because they destabilize the Bam complex but rather because they disrupt this coordination. Our model of BamA-BamD interactions regulating conformation in response to proper substrate interaction is reminiscent of conformational changes the secretory (Sec) machinery undergoes after signal sequence recognition that ensure protein quality control.
Peripheral hepatojejunostomy: a last resort palliative solution in Greece during the economic crisis
Authors: Sotiropoulos Georgios C , Spartalis Eleftherios , Machairas Nikolaos , Kouraklis Gregory
Published: August 2017

The geographical distribution of Greece and the growing proportion of uninsured patients make imperative the need for effective and efficient palliative solutions regarding obstructive jaundice due to hepatic malignancy, while repeated endoscopic interventions and all associated materials are either not accessible to the whole population or not even available on a daily basis due to the economic crisis and the difficulties on the hospital supply. On this basis, palliative hepatojejunostomy, introduced more than 50 years ago, could be revisited in the Greek reality in very selected cases and under these special circumstances. We report on two patients with locally advanced hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma, respectively, who were treated with a combination of double hepaticojejunostomy with peripheral hepatojejunostomy or peripheral hepatoejunostomy alone, respectively. Both patients experienced an adequate decompression of the biliary tract over more than a year. Palliative hepatojejunostomy could be an ultimate solution for selected patients and circumstances in Greece during the economic crisis.
Transient clinical improvement of a mitochondrial neurogastrointestinal encephalomyopathy-like syndrome after allogeneic haematopoietic stem cell transplantation
Authors: Baker Malcolm Kevin , Schutte Clara Maria , Ranchhod Neelay , Brittain David , van Rensburg J E
Published: August 2017

Mitochondrial neurogastrointestinal encephalopathy (MNGIE), usually an autosomal-recessive inherited condition, causes gastrointestinal dysmotility, ophthalmoplegia, ptosis, leukoencephalopathy and neuropathy. The chromosome 22 disorder, due to mutations in the nuclear gene TYMP encoding thymidine phosphorylase (TP), leads to the accumulation of thymidine and deoxyuridine, with mitochondrial dysfunction.

This report describes a patient with an MNGIE-like syndrome with a heterozygous TYMP mutation who showed marked, but transient improvement postallogeneic haematopoietic stem cell transplantation (HSCT).

The patient, showing ptosis and ophthalmoplegia, was initially managed for myasthenia gravis. She developed gastrointestinal symptoms, dysarthria, dysphagia and weakness, and MNGIE was considered due to its low TP levels and improvement after platelet transfusions. She underwent HSCT, with dramatic improvement, but regressed 18 months later despite normal TP levels, platelet counts and full chimerism.

MNGIE may encompass a spectrum of disorders. TP deficiency alone is unlikely to explain all clinical signs, and other factors, including the possible development of anti-TP antibodies, which may play a role in the pathophysiology.
Isolated third nerve palsy: a rare neurological presentation of Burkitt's lymphoma
Authors: Kalantri Siddhesh Arun , Nayak Akshatha , Datta Saikat , Bhattacharyya Maitreyee
Published: August 2017

Lymphoma patient presenting with isolated third nerve palsy is relatively rare, and diagnosis of underlying disease may be challenging. Until this date, less than 20 cases have been described in the literature. This is the case of a 3-year-old boy who presented to neurologist with ptosis of left eye for 8 days. On examination, abdominal mass was detected, and the child was referred to paediatric surgery department. Laparotomy and excision of the mass was done. Histopathology and immunohistochemistry of the mass confirmed it to be a case of Burkitt's lymphoma. At this point, the patient was referred to haematology department. Contrast-enhanced CT brain showed infiltration around left cavernous sinus. Patient was treated with two cycles of R-CODOX-M/R-IVAC. Ptosis improved completely within few days of starting chemotherapy. Follow-up positron emission tomography CT scan done after the second cycle of chemotherapy revealed no metabolically active disease.
Tuberculous pericarditis treated with steroid in a dialysis patient
Authors: Aoyama Rie , Ishikawa Joji , Harada Kazumasa , Tukada Yayoi
Published: August 2017

Mycobacterium tuberculosishas spread worldwide and its mortality rate had been very high. The prevention technology and antituberculosis (TB) chemotherapy has improved its prognosis. However, immunocompromised patients, such as those who had HIV infection, older age and on haemodialysis, are still at high risk of TB infection. TB pericarditis is a common cause of constrictive pericarditis and its mortality remains high. Early diagnosis and initiation of appropriate therapy are critical to improve mortality. Additionally, detection of an elevation in the adenosine deaminase level in pericardial effusion is reported to be useful. We report the case of an immunocompromised patient with TB pericarditis, and steroid therapy could prevent him from progressing to constrictive pericarditis. The adenosine deaminase value of pericardial effusion was so helpful that we could promptly make clinical and therapeutic decisions.
The non-resolving lung cavity: a case of pulmonary cystic echinococcosis
Authors: Mifsud Simon , Schembri Emma Louise , Gauci Jonathan , Mizzi Adrian , Mallia Azzopardi Charles , Micallef Josef
Published: August 2017

The authors report a case of a 20-year-old woman who was diagnosed with pulmonary cystic echinococcosis. She was admitted to hospital with a 1-week history of unresolving cough, coloured sputum with occasional haemoptysis and fever despite oral antibiotics. Radiology revealed a cavitating right lower lobe lung abscess. After 4 weeks of treatment, follow-up radiology showed incomplete resolution. Bronchoscopy revealed a white, avascular cystic lesion in the right lower lobe and serology testing forEchinococcus granulosuswas positive. Repeat imaging eventually confirmed the cystic lesion with the 'air bubble'sign. A thorough travel history, a high index of clinical suspicion and close follow-up are essential in making a diagnosis of pulmonary cystic echinococcosis.
Reversible central neural hyperexcitability: an electroencephalographic clue to hypocalcaemia
Authors: Patel Bhagyadhan A , Chakor Rahul T , Kothari Kaumil V , Nadaf Swaleha
Published: August 2017

A 23-year-old male patient presented with cognitive decline and seizures. Examination revealed Chvostek's and Trousseau's signs. Investigations revealed hypocalcaemia, hyperphosphatemia and normal intact parathyroid hormone levels. Imaging showed calcifications in bilateral basal ganglia, thalamus and dentate nuclei. Interictal electroencephalogram showed theta range slowing of background activity and bilateral temporo-occipital, irregular, sharp and slow wave discharges, which accentuated during hyperventilation, photic stimulation and eye closure. Appearance of epileptiform discharges after eye closure, hyperventilation and photic stimulation may suggest presence of central neural hyperexcitability due to hypocalcaemia. These features may be an equivalent of peripheral neuromuscular hyperexcitability (Chvostek's and Trousseau's signs) that occurs in hypocalcaemia. The clinical and electroencephalographic features completely reversed with correction of serum calcium without antiepileptic medications. It is important for clinicians to recognise these reversible changes, as it can help to avoid misdiagnosis and long-term administration of antiepileptic becomes unnecessary.
Individuals at high risk for type 2 diabetes invited to a lifestyle program: characteristics of participants versus non-participants (the HUNT Study) and 24-month follow-up of participants (the VEND-RISK Study)
Authors: Følling Ingrid Sørdal , Kulseng Bård , Midthjell Kristian , Rangul Vegar , Helvik Anne-S
Published: August 2017

Objective

Prevention of type 2 diabetes mellitus is possible through lifestyle programs, but the effect depends on the program's content, resources, and setting. Lifestyle programs are often confronted with high rates of non-participation and attrition. This study invited individuals at high risk for type 2 diabetes to a lifestyle program in the Norwegian primary healthcare setting. The aims were to investigate possible differences in characteristics between participants and non-participants and to study the effect of the lifestyle program at 24-month follow-up for participants.

Research design and methods

Individuals identified at high risk for type 2 diabetes during the third survey of the Nord-Trøndelag Health Study (HUNT3) from two municipalities (n=332) were invited to a lifestyle program (the VEND-RISK Study). A cross-sectional design was used to explore if the participants’ characteristics differed from non-participants. A non-randomized, single-arm, pre–post examination was used to examine the effect of the lifestyle program on participants’ characteristics at 24-month follow-up.

Results

Of all individuals at high risk for type 2 diabetes invited to the lifestyle program, 86% (287/332) declined to participate. Non-participating women had fewer years of education (p<0.001), compared with participating women. For men, no differences were seen between non-participants and participants. Among all participants (n=45) at 24-month follow-up, none had developed type 2 diabetes, and HbA1c(p<0.001) had decreased significantly. There was a small reduction in mean body mass index from baseline to 24 months that was not statistically significant. For women, waist circumference (−4.0 cm, p<0.001) decreased significantly.

Conclusions

Future research regarding individuals at high risk for type 2 diabetes in the primary healthcare lifestyle program should focus on how to promote recruitment of women with low education. Participants attending this study's lifestyle program improved their cardiometabolic markers.

Clinical trials registration

NCT01135901; Results.
Polyethylene glycol intestinal lavage in addition to usual antibiotic treatment for severeClostridium difficilecolitis: a randomised controlled pilot study
Authors: McCreery Greig , Jones Philip M , Kidane Biniam , DeMelo Vanessa , Mele Tina
Published: August 2017

Introduction

Clostridium difficileinfections (CDI) are common, costly and potentially life threatening. Most CDI will respond to antibiotic therapy, but 3%–10% of all patients with CDI will progress to a severe, life-threatening course. Complete removal of the large bowel is indicated for severe CDI. However, the 30-day mortality following surgical intervention for severe CDI ranges from 20% to 70%. A less invasive approach using surgical faecal diversion and direct colonic lavage with polyethylene glycol (PEG) and vancomycin has demonstrated a relative mortality reduction of approximately 50%. As an alternative to these operative approaches, we propose to treat patients with bedside intestinal lavage with PEG and vancomycin instillation via nasojejunal tube, in addition to usual antibiotic management. Preliminary data collected by our research group are encouraging.

Methods and analysis

We will conduct a 1-year, single-centre, pilot randomised controlled trial to study this new treatment strategy for patients with severe CDI and additional risk factors for fulminant or complicated infection. After informed consent, patients with severe-complicated CDI without immediate indication for surgery will be randomised to either usual antibiotic treatment or usual antibiotic treatment with the addition of 8 L of PEG lavage via nasojejunal tube. This pilot trial will evaluate our eligibility and enrolment rate, protocol compliance and adverse event rates and provide further data to inform a more robust sample size calculation and protocol modifications for a definitive multicentre trial design. Based on historical data, we anticipate enrolling approximately 24 patients during the 1-year pilot study period.

As a pilot study, data will be reported in aggregate. Between-group differences will be assessed in a blinded fashion for evidence of harm, and to further refine our sample size calculation.

Ethics and dissemination

This study protocol has been reviewed and approved by our local institutional review board. Results of the pilot trial and subsequent main trial will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT02466698; Pre-results.