bluuebunny/crossref_metadata_2025 huggingface dataset:
Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition
Authors: Chaudhary Amrita , Bag Swarnendu , Barui Ananya , Banerjee Provas , Chatterjee Jyotirmoy
Published: April 2015

Honey is known as a popular healing agent against tropical infections and wounds. However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing under hypoxic condition is still not explored. In this study, we examined whether honey dilution have wound healing potential under hypoxic stress. The antioxidant potential and healing efficacy of honey dilution on in vitro wound of human epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2), and normoxia is explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the changes in cellular function was observed microscopically. Further, the cell proliferation, migration, cell–cell adhesion, and relevant gene expression were studied by flow cytometry, migration/scratch assay, immunocytochemistry, and reverse transcription‐polymerase chain reaction, respectively. The expression pattern of cardinal molecular features viz. E‐cadherin, cytoskeletal protein F‐actin, p63, and hypoxia marker Hif 1α were examined. Honey dilution in 0.1% v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%). Its wound healing potential was quantified by immunocytochemistry and real‐time PCR for the associated molecular features that were responsible for cell proliferation and migration. Our data showed that honey dilution can be effective in hypoxic wound healing. Additionally, it reduced superoxide generation and supplied favorable bioambience for cell proliferation, migration, and differentiation during hypoxic wound healing. These findings may reveal the importance of honey as an alternative and cost effective therapeutic natural product for wound healing in hypoxic condition.
An open multicenter comparative randomized clinical study on chitosan
Authors: Mo Xiaohui , Cen John , Gibson Elaine , Wang Robin , Percival Steven L.
Published: April 2015

Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next‐generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management of chronic wounds.
Targeted metabolic profiling of wounds in diabetic and nondiabetic mice
Authors: Sood Ravi F. , Gu Haiwei , Djukovic Danijel , Deng Lingli , Ga Maricar , Muffley Lara A. , Raftery Daniel , Hocking Anne M.
Published: April 2015

While cellular metabolism is known to regulate a number of key biological processes such as cell growth and proliferation, its role in wound healing is unknown. We hypothesized that cutaneous injury would induce significant metabolic changes and that the impaired wound healing seen in diabetes would be associated with a dysfunctional metabolic response to injury. We used a targeted metabolomics approach to characterize the metabolic profile of uninjured skin and full‐thickness wounds at day 7 postinjury in nondiabetic (db/‐) and diabetic (db/db) mice. By liquid chromatography mass spectrometry, we identified 129 metabolites among all tissue samples. Principal component analysis demonstrated that uninjured skin and wounds have distinct metabolic profiles and that diabetes alters the metabolic profile of both uninjured skin and wounds. Examining individual metabolites, we identified 62 with a significantly altered response to injury in the diabetic mice, with many of these, including glycine, kynurenate, and OH‐phenylpyruvate, implicated in wound healing for the first time. Thus, we report the first comprehensive analysis of wound metabolic profiles, and our results highlight the potential for metabolomics to identify novel biomarkers and therapeutic targets for improved wound healing outcomes.
Endothelial‐to‐mesenchymal transition induced by Wnt 3a in keloid pathogenesis
Authors: Lee Won Jai , Park Ji Hun , Shin Jung U. , Noh Hyun , Lew Dae Hyun , Yang Woo Ick , Yun Chae Ok , Lee Kwang Hoon , Lee Ju Hee
Published: April 2015

Endothelial‐to‐mesenchymal transition is a phenotypic conversion characterized by down‐regulation of vascular endothelial markers and the acquisition of a mesenchymal phenotype. We hypothesized that keloid fibroblasts are of endothelial origin and that endothelial‐to‐mesenchymal transition substantially contributes to collagen accumulation during the development and progression of keloids. Wingless protein (Wnt‐3a) protein expression was examined using immunohistochemistry in keloid tissues. Human dermal microvascular endothelial cells (HDMECs) were treated with Wnt‐3a. mRNA and protein expression of endothelial (vascular endothelial cadherin) and mesenchymal (vimentin, snail family transcription factor [slug], and α‐smooth muscle actin) cell markers were measured using real‐time RT‐PCR and immunocytochemistry, respectively. Additionally, coexpression of CD31 (cluster of differentiation 31), and endothelial cell marker, and vimentin in the vascular endothelium of keloid tissues was examined using immunofluorescence. Wnt‐3a overexpression was observed in human keloid tissues. Wnt‐3a treatment significantly reduced vascular endothelial cadherin mRNA expression and induced vimentin and slug mRNA expression in HDMECs. HDMECs became spindle‐shaped and exhibited reduced expression of CD31 and increased expression of vimentin, slug, and α‐smooth muscle actin. Moreover, coexpression of CD31 and vimentin was observed in the dermal vascular endothelium of keloid tissues from two patients with clinically active keloids. In conclusion, transient conversion of HDMECs to a mesenchymal phenotype may contribute to dermal fibrosis of keloid and hypertrophic scars.
Evaluating the Performance of Traffic Flow in Four Intersections and Two Roundabouts in Petaling Jaya and Kuala Lumpur Using Sidra 4.0 Software
Authors: Mohamed Irtema Hamza Imhimmed , Ismail Amiruddin , Ismael Albrka Shaban , Ladin Mohd Azizul , A. M. Yahia Hussin
Published: April 2015

Delays represent one of the indirect costs in terms of frustration, loss of time and discomfort to the drivers. On the other hand, it represents a direct cost in terms of fuel consumption/wastage on road networks during idleness and inactivity. Extreme delay at signalized intersections reflects the incompetence in the signal timing because of consecutive signalized intersections on the particular site. The traffic parameters performance is not a feasible method or practice. Furthermore, one of the significant ways to improve the performance of the network is by coordinating traffic signal in intersections. This study was done to highlight the ability of improving the level of service (LOS) of four intersections; two of them with four legs and two with three legs as well as two roundabouts in Kuala Lumpur and Petaling Jaya using SIDRA software version 4.0. In addition, the study aims to compare the results between each peak hour in terms of percentage of change in the variables and the delay. Moreover, consideration of geometric delay should be taken into account when comparing delays in peak hours in the morning and the evening peak hours. The results obtained show that the morning period is better than the evening period for the value of delay, queue, journey time and speed that was obtained from practical measuring in the study area. The average reduction of delay in the study area before and after optimization of SIDRA software is from 3489 Sec to 1571 Sec in the morning period as well as 5093 Sec to 1663 Sec in the evening period. The percentage of reduction was about 45% and 33% -respectively.
Analysis of Rainfall Effect to Slope Stability in Ulu Klang, Malaysia
Authors: Mukhlisin Muhammad , Matlan Siti Jahara , Ahlan Mohamad Jaykhan , Taha Mohd Raihan
Published: April 2015

Malaysia is a country that is located near the equator line with tropical climates which receives high abundant rainfall, averaging 2,400mm annually. This makes Malaysia prone to the landslide events as rainfall is one of the main triggering factors that can cause landslide. Landslides in Malaysia are mainly attributed to frequent and prolonged rainfalls, in many cases associated with monsoon rainfalls. Of these, Ulu Klang area has received the most exposure. The area has constantly hit by fatal landslides since December 1993. This paper is aimed to investigate the correlation between the effective working rainfall and soil water index (SWI) methods with the landslide events in Ulu Klang, Malaysia. In this study 15 landslide events that occurred in Ulu Klang areas between years 1993 to 2012 were investigated and analyzed using rainfall threshold based on effective working rainfall and soil water index (SWI) methods. The analysis results showed that these methods are significant tools that can be used to identify the rainfall critical threshold of landslide event.
Gravitational Search Algorithm Optimization for PID Controller Tuning in Waste-water Treatment Process
Authors: Aziz Mohamad Saiful Islam , Nawawi Sophan Wahyudi , Sudin Shahdan , Abdul Wahab Norhaliza , Faramarzi Mahdi , Md. Yusof Masdinah Alauyah
Published: April 2015

This paper presents a new approach of optimization technique in the controller parameter tuning for waste-water treatment process (WWTP) application. In the case study of WWTP, PID controller is used to control substrate (S) and dissolved oxygen (DO) concentration level. Too many parameters that need to be controlled make the system becomes complicated. Gravitational Search Algorithm (GSA) is used as the main method for PID controller tuning process. GSA is based on Newton's Law of Gravity and mass interaction. In this algorithm, the searcher agents survey the masses that interact with each other using law of gravity and law of motion. For WWTP system, the activated sludge reactor is used and this system is multi-input multi-output (MIMO) process. MATLAB is used as the platform to perform the simulation, where this optimization is compared to other established optimization method such as the Particle Swarm Optimization (PSO) to determine whether GSA has better features compared to PSO or vice-versa. Based on this case-study, the results show that transient response of GSA-PID was 20%-30% better compared to transient response of the PSO-PID controller.
Microwave Tomography Application and Approaches – A Review
Authors: Rahiman Mohd Hafiz Fazalul , Wan Kiat Thomas Tan , Ping Jack Soh , Abdul Rahim Ruzairi
Published: April 2015

The objective of this paper is to review microwave tomography based on its field, application and antennas approaches. Researches on microwave tomography system have been done unceasingly for several decades especially in determine the dielectric properties for the material. Firstly, the dielectric properties and its influencing factors will be briefly described. Besides, although it has the potential to overcome other process tomography system, it still have some drawbacks. So, the general advantages and disadvantages are listed. Next, survey on the application of microwave tomography and type of antennas used will be discussed. Followed by the trend for the future.
A Review on The Exploration of Nanomaterials Application in Pavement Engineering
Authors: Abdullah Mohd Ezree , Ahmad Zamhari Kemas , Buhari Rosnawati , Mohd Kamaruddin Nurul Hidayah , Nayan Nafarizal , Hainin Mohd Rosli , Abdul Hassan Norhidayah , Putra Jaya Ramadhansyah , Md. Yusoff Nur Izzi
Published: April 2015

In order to improve the performance of asphalt mixture, the virgin asphalt binder needs to be modified with suitable modifiers. There are various types of modifiers available in market and it is clearly stated and established in most of pavement standard specification. Nowadays, pavement technologist and researchers had put their interests on nanotechnology and they had found that polymeric nanocomposites have shown its effectiveness through the modification of virgin asphalt binder with certain portion of nanomaterials. In addition, many studies have demonstrated that nanomaterials have significant effects in improving the engineering properties of asphalt binder and mixture. Therefore, a thorough literature review on the current research of nanomaterials in pavement engineering for the past decades can enhance understanding and guaranteed something beneficial findings in the future. This paper described the theory of nanotechnology and its historical development including the method used among researchers in evaluation the structural and morphological characteristics of modified binder with nanoparticles. Also, the effect of different types of nanoparticles, suitable dosages, modifying procedures, problems and benefits on asphalt binder and mixture were explained. It is expected that in future the implementations of nanotechnology would have major impacts for better pavement performance.
Modelling of Pedestrian Speed-Density and Volume-Density Relationships in Outdoor Walkways
Authors: Mohammed Alhassan Hashim , Mashros Nordiana
Published: April 2015

The aim of this study was to model pedestrian flow parameters needed in the design of pedestrian facilities. The study also characterized the flow with a view to understanding pedestrian interaction problems especially with regards to their congestion. Twenty-five locations across Kano metropolis were selected for study, thirteen locations from the city district while twelve sites were chosen from the Waje district. All the sites were high flow pedestrian locations that met the study objectives. The data was categorized into four; young male, adult male, young female and adult female. The results indicated that adult women walked faster than their male counterparts in the City district while young males were faster than the female. The adult female recorded an average speed of 73.90 m/min against the speed of 71.30 m/min for the adult male. The average characteristics of the pedestrian in the city district are speed 67.30 m/min; density 11.23 Ped/m2 and volume 33.60 Ped/m/min. In the Waje district, however, the male pedestrian whether adult or young walked faster than their corresponding female counterparts with speed of 71.45 m/min for the adult male and 59.90 m/min for the adult female. The young male was faster than the young female by 17.9%. The average pedestrian flow parameters for the Waje district indicated a combine speed of 60.21 m/min; density of 8.72 Ped/m2 and volume of 30.92 Ped/m/min. The pedestrians in the city district had a higher flow rate, higher density and higher speed than those of the Waje district. This means the city district is a little more concentrated than the Waje district in terms of pedestrian flow. The aggregate average flow parameters of pedestrians in the metropolitan area gave the following parameters: speed 68.92 m/min; density 10.03 Ped/m2 and volume 32.33 Ped/m/min. The predictive models for Kano showed a free flow speed of 59.55 m/min and a maximum flow rate of 73.0 Ped/m/min. Comparing the Kano pedestrian model with other countries it was found that the Kano pedestrian walked slower than pedestrians from Singapore and the United States
Plastic Ploughing of a Sinusoidal Asperity on a Rough Surface
Authors: Song H. , Dikken R. J. , Nicola L. , Van der Giessen E.
Published: April 2015

Part of the friction between two rough surfaces is due to the interlocking between asperities on opposite surfaces. In order for the surfaces to slide relative to each other, these interlocking asperities have to deform plastically. Here, we study the unit process of plastic ploughing of a single micrometer-scale asperity by means of two-dimensional dislocation dynamics simulations. Plastic deformation is described through the generation, motion, and annihilation of edge dislocations inside the asperity as well as in the subsurface. We find that the force required to plough an asperity at different ploughing depths follows a Gaussian distribution. For self-similar asperities, the friction stress is found to increase with the inverse of size. Comparison of the friction stress is made with other two contact models to show that interlocking asperities that are larger than ∼2 μm are easier to shear off plastically than asperities with a flat contact.
Optomechanics of Soft Materials
Authors: Bai Ruobing , Suo Zhigang
Published: April 2015

Some molecules change shape upon receiving photons of certain frequencies, but here we study light-induced deformation in ordinary dielectrics with no special optical effects. All dielectrics deform in response to light of all frequencies. We derive a dimensionless number to estimate when light can induce large deformation. For a structure made of soft dielectrics, with feature size comparable to the wavelength of light, the structure shapes the light, and the light deforms the structure. We study this two-way interaction between light and structure by combining the electrodynamics of light and the nonlinear mechanics of elasticity. We show that optical forces vary nonlinearly with deformation and readily cause optomechanical snap-through instability. These theoretical ideas may help to create optomechanical devices of soft materials, complex shapes, and small features.
The SPEEDTRONIC Mark IV Control™, a Distributed Fault Tolerant Gas Turbine Control System
Authors: Johnson D. , Gilbert K. E. , Buckley L. P.
Published: April 2015

Greatly improved availability is the primary design goal of the SPEEDTRONTC Mark IV Gas Turbine control. It achieves this goal by distributing control functions among four microcomputers: three are identical control sections, and the fourth handles communications. Powerful on-line diagnostics indicate which section is faulty, down to the replaceable element. Panel repair is effected with the gas turbine running. Mean time to repair is predicted to be three to four hours. The prediction is that the SPEEDTRONIC Mark IV control will not cause a plant shut down more often than once in ten years. In addition, the system has capacity for redundant sensor inputs, which significantly reduces forced outages caused by faulty sensors. Information on how these results were accomplished is presented in the paper, along with a description of the initial experiences running gas turbines with the new system.
Vibration Analysis of Radial Compressor Impellers
Authors: Wachter J. , Celikbudak H.
Published: April 2015

There are many problems facing the designers of turbomachines with the demand for ever increasing capabilities and reliability. One problem that requires considerable attention is the vibration characteristics of some components. It is object of this work to determine the dynamic behavior, namely natural frequencies, mode shapes of a centrifugal impeller which are being important design parameters in order to avoid costly failures in the development phase.

This work divides into three sections. First, a Finite Element structural dynamic analysis is presented. Then experimental procedure used to determine the natural frequencies and mode shapes is described together with the comparison of the results obtained both theoretically through FEM and experimentally.

Finally, interferometric holography technique is used as a means for obtaining the dynamic behavior of the impeller.
Effects of Anomalous Rotor Joints on Turbomachine Dynamics
Authors: Klompas N.
Published: April 2015

Mechanisms simulating rotor joint restoring moments different from the common axisymmetric elastic hinge are derived and their effects on the dynamics of a complete turbomachine are calculated by impressing equivalent perturbing moments. A mechanism for locking subsynchronous whirl to a fractional frequency is described and supporting experimental observations are discussed. Sample analysis shows the possibility of self-sustained synchronous whirl due to preload asymmetry.
A Comparative Study of the Influence of Different Means of Turbine Cooling on Gas Turbine Performance
Authors: Louis J. F. , Hiraoka K. , El Masri M. A.
Published: April 2015

A comparative study of the influence of different means of turbine cooling on the thermodynamic efficiency and specific work of gas turbines is presented. A common general model of a simple open cycle gas turbine is used to compare the performance of turbines using different types of cooling; internal convection and impingement by air, film cooling by air, internal convection and impingement by steam, film cooling by steam and closed loop cooling by water. The results are also compared to the previously published results of the analysis of open loop water cooled gas turbines. The model evaluates the efficiency and specific work of simple cycle gas turbines as it is influenced by mixing losses of coolant with combustion gases, pumping work of coolant and heat transfer from the expanding gas. The study is performed in terms of dimensionless variables in order to achieve generality and to provide useful design guidelines and insights. Blades internally cooled by convection and impingement are treated as heat exchangers operating at constant metal temperature and the coolant exit temperature is simply expressed as a function of a heat exchanger effectiveness, an independent parameter which is normally a function of the intricacy of the layout of the cooling passages. The coolant requirements and heat transfer with film cooling are determined using a dimensionless correlation derived experimentally at M.I.T. Sample calculations give the optimum turbine inlet temperature of thermodynamic efficiency and specific work for different pressure ratios and typical dimensionless numbers. The data on specific work are significant because they can be readily used in evaluations of a given type of gas turbine in a combined cycle. The sensitivity of the efficiency and specific work to each key input parameter is reported.

The use of superheated steam as a coolant can provide some performance advantages since the steam raised in a waste heat boiler expands with the combustion gases, increases the turbine mass flow and also provides a certain amount of heat regeneration. Performance results are also reported for this steam cooled gas turbine operating with mixed working fluid.
X-Ray Tomography Applied to NDE of Ceramics
Authors: Kress J. W. , Feldkamp L. A.
Published: April 2015

An x-ray radiographic NDE system specifically suited to three-dimensional tomographic reconstruction is described. The results of two applications of the system are discussed. The first is the reconstruction of a section of a ceramic gas turbine rotor blade. This demonstrates the system’s ability to reconstruct parts with complex external shape. In the second, an assembly of ceramic components containing a 50 μm gap is examined. The 50 μm gap is detected. This work was supported in part by the Office of Naval Research under contract N00014-78-C-0714.
Gas Turbine Installation and Foundation Repair With Epoxy Resins
Authors: Wilson J. Murray
Published: April 2015

Epoxy resins are not just replacements for concrete and cement grouts, they offer the opportunity for completely new foundation/gas turbine interface designs. As a substitute for steel chocks, epoxy resin ones give perfect fit, high holding force and good thermal insulation, while eliminating the need for soleplates or rails.
A Test Facility for the Investigation of Steady and Unsteady Transonic Flows in Annular Cascades
Authors: Bölcs Albin
Published: April 2015

A unique non-rotating aerodynamic test facility is presented. It is designed for steady and unsteady transonic flow investigations in annular cascades. The fundamental advantage of this vehicle design, compared to a linear cascade facility, is the absence of boundary disturbances in the cascade and the self-adjustment of the flow periodicity. The downstream flow conditions can therefore be adjusted by the backpressure.

The nozzle consists of a radial-axial section, in which spiral axisymetric flow is generated. With the adjustment of the total pressure and swirl angles in two separate distributors, a continuous variation of Mach number between 0<M<1,4 and flow angles between 12°<β<70° (from tangential) can be obtained.

Further regulation of the flow quantities in the two separate distributors and boundary layer suction permits a continuous spanwise variation of the velocity and flow angle in the test section.
Team-Sport Athletes’ Improvement of Performance on the Yo-Yo Intermittent Recovery Test Level 2, but Not of Time-Trial Performance, With Intermittent Hypoxic Training
Authors: Inness Mathew W.H. , Billaut François , Aughey Robert J.
Published: April 2015

Purpose:

To determine the time course for physical-capacity adaptations to intermittent hypoxic training (IHT) in team-sport athletes and the time course for benefits remaining after IHT.

Methods:

A pre–post parallel-groups design was employed, with 21 Australian footballers assigned to IHT (n = 10) or control (CON; n = 11) matched for training load. IHT performed eleven 40-min bike sessions at 2500-m altitude over 4 wk. Yo-Yo Intermittent Recovery Test level 2 (Yo-Yo IR2) was performed before; after 3, 6, and 11 IHT sessions; and 30 and 44 d after IHT. Repeated time trials (2- and 1-km TTs, with 5 min rest) were performed before, after, and 3 wk after IHT. Hemoglobin mass (Hbmass) was measured in IHT before and after 3, 6, 9, and 11 sessions.

Results:

Baseline Yo-Yo IR2 was similar between groups. After 6 sessions, the change in Yo-Yo IR2 in IHT was very likely higher than CON (27% greater change, effect size 0.77, 90% confidence limits 0.20;1.33) and likely higher 1 d after IHT (23%, 0.68, 0.05;1.30). The IHT group’s change remained likely higher than CON 30 d after IHT (24%, 0.72, 0.12;1.33) but was not meaningfully different 44 d after (12%, 0.36, –0.24;0.97). The change in 2-km TT performance between groups was not different throughout. For 1-km TT, CON improved more after IHT, but IHT maintained performance better after 3 wk. Hbmass was higher after IHT (2.7%, 0.40, –0.40;1.19).

Conclusion:

Short-duration IHT increased Yo-Yo IR2 compared with training-load-matched controls in 2 wk. An additional 2 wk of IHT provided no further benefit. These changes remained until at least 30 d posttraining. IHT also protected improvement in 1-km TT.
The Effect of Sport Video Gaming on Sport Brand Attitude, Attitude Strength, and the Attitude-Behavior Relationship
Authors: Kim Yongjae , Ross Stephen
Published: April 2015

This study examined the impact of repetitive sport video gaming on sport brand attitudes, attitude strength (e.g., attitude accessibility and confidence), and the attitude-behavior relationship. An experiment was designed to demonstrate the attitude-behavior consistency in a hypothetical choice context. The results indicated that repeated exposure to sport video games emulating a real-life sport influences sport attitude and its strength, and subsequently hypothetical choice behavior. The sport attitudes formed on virtual sport experience (e.g., playing sport video games repetitively) are as accessible and held with the same degree of confidence as those formed on direct experience (e.g., watching a sport on TV). The findings also confirmed the moderating effect of attitude confidence on the attitude-behavior relationship.
The supramammillary nucleus and the claustrum activate the cortex during REM sleep
Authors: Renouard Leslie , Billwiller Francesca , Ogawa Keiko , Clément Olivier , Camargo Nutabi , Abdelkarim Mouaadh , Gay Nadine , Scoté-Blachon Céline , Touré Rouguy , Libourel Paul-Antoine , Ravassard Pascal , Salvert Denise , Peyron Christelle , Claustrat Bruno , Léger Lucienne , Salin Paul , Malleret Gael , Fort Patrice , Luppi Pierre-Hervé
Published: April 2015

Plasticity and cortical activation during REM sleep is shown by a subset of cortical and hippocampal neurons.
By-product metals are technologically essential but have problematic supply
Authors: Nassar N. T. , Graedel T. E. , Harper E. M.
Published: April 2015

Metals that are obtained largely or entirely as by-products are essential to modern technology, but their supplies may be constrained due to a variety of factors.
Life and death of a single catalytic cracking particle
Authors: Meirer Florian , Kalirai Sam , Morris Darius , Soparawalla Santosh , Liu Yijin , Mesu Gerbrand , Andrews Joy C. , Weckhuysen Bert M.
Published: April 2015

Macropore blocking through metal deposition and intrusion of particles is a major deactivation mechanism in FCC catalysts essential to gasoline production.
Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation
Authors: Tang Jun , Lobatto Mark E. , Hassing Laurien , van der Staay Susanne , van Rijs Sarian M. , Calcagno Claudia , Braza Mounia S. , Baxter Samantha , Fay Francois , Sanchez-Gaytan Brenda L. , Duivenvoorden Raphaël , Sager Hendrik B. , Astudillo Yaritzy M. , Leong Wei , Ramachandran Sarayu , Storm Gert , Pérez-Medina Carlos , Reiner Thomas , Cormode David P. , Strijkers Gustav J. , Stroes Erik S. G. , Swirski Filip K. , Nahrendorf Matthias , Fisher Edward A. , Fayad Zahi A. , Mulder Willem J. M.
Published: April 2015

Nanoparticle-based delivery of simvastatin inhibits plaque macrophage proliferation in apolipoprotein E–deficient mice.
A
Candida albicans
CRISPR system permits genetic engineering of essential genes and gene families
Authors: Vyas Valmik K. , Barrasa M. Inmaculada , Fink Gerald R.
Published: April 2015

CRISPR simplifies genetic engineering of the human fungal pathogen
Candida albicans
.
miRNAs encode miPEPs
Authors: Prabakaran Sudhakaran
Published: April 2015

Precursors of microRNAs encode peptides that regulate the production of the mature microRNA.
Young at heart: Restoring cardiac function in children
Authors: LaMarco Kelly
Published: April 2015

The growth factor neuregulin stimulates heart muscle repair in newborn mice and heart muscle from human infants if given during a specific therapeutic time period.
Fast Hepatitis C Virus RNA Elimination and NS5A Redistribution by NS5A Inhibitors Studied by a Multiplex Assay Approach
Authors: Liu Dandan , Ji Juan , Ndongwe Tanya P. , Michailidis Eleftherios , Rice Charles M. , Ralston Robert , Sarafianos Stefan G.
Published: April 2015

While earlier therapeutic strategies for the treatment of hepatitis C virus (HCV) infection relied exclusively on interferon (IFN) and ribavirin (RBV), four direct-acting antiviral agents (DAAs) have now been approved, aiming for an interferon-free strategy with a short treatment duration and fewer side effects. To facilitate studies on the mechanism of action (MOA) and efficacy of DAAs, we established a multiplex assay approach, which employs flow cytometry, a
Gaussia
luciferase reporter system, Western blot analysis, reverse transcription-quantitative PCR (RT-qPCR), a limited dilution assay (50% tissue culture infectious dose [TCID
50
]), and an image profiling assay that follows the NS5A redistribution in response to drug treatment. We used this approach to compare the relative potency of various DAAs and the kinetics of their antiviral effects as a potential preclinical measure of their potential clinical utility. We evaluated the NS5A inhibitors ledipasvir (LDV) and daclatasvir (DCV), the NS3/4A inhibitor danoprevir (DNV), and the NS5B inhibitor sofosbuvir (SOF). In terms of kinetics, our data demonstrate that the NS5A inhibitor LDV, followed closely by DCV, has the fastest effect on suppression of viral proteins and RNA and on redistribution of NS5A. In terms of MOA, LDV has a more pronounced effect than DCV on the viral replication, assembly, and infectivity of released virus. Our approach can be used to facilitate the study of the biological processes involved in HCV replication and help identify optimal drug combinations.
A Thorough QT Study To Evaluate the Effects of Therapeutic and Supratherapeutic Doses of Delafloxacin on Cardiac Repolarization
Authors: Litwin Jeffrey S. , Benedict Michael S. , Thorn Michael D. , Lawrence Laura E. , Cammarata Sue K. , Sun Eugene
Published: April 2015

A randomized, double-blind, placebo-controlled, 4-period crossover study was conducted in 52 healthy adults to assess the effect of delafloxacin on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using Fridericia's formula (QTcF), was determined predose and at 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 12, 18, and 24 h after dosing with delafloxacin at 300 mg intravenously (i.v.; therapeutic), delafloxacin at 900 mg i.v. (supratherapeutic), moxifloxacin at 400 mg orally (p.o.; positive control), and placebo. The pharmacokinetic profile of delafloxacin was also evaluated. At each time point after delafloxacin administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms (maximum, 3.9 ms at 18 h after dosing), indicating an absence of a clinically meaningful increase in the QTc interval. The lower limit of the 90% CI of ΔΔQTcF for moxifloxacin versus placebo was longer than 5 ms at all 5 time points selected for assay sensitivity analysis, demonstrating that the study was adequately sensitive to assess QTc prolongation. There was no positive relationship between delafloxacin plasma concentrations and ΔΔQTcF. Treatment-emergent adverse events (AEs) were more frequent among subjects receiving a single supratherapeutic dose of 900 mg delafloxacin. There were no deaths, serious AEs, or AEs leading to study discontinuation and no clinically meaningful abnormalities in laboratory values or vital signs observed at any time point after any dose of the study drug.
Enantiomers of Nifurtimox Do Not Exhibit Stereoselective Anti-Trypanosoma cruzi Activity, Toxicity, or Pharmacokinetic Properties
Authors: Moraes Carolina B. , White Karen L. , Braillard Stéphanie , Perez Catherine , Goo Junghyun , Gaspar Luis , Shackleford David M. , Cordeiro-da-Silva Anabela , Thompson R. C. Andrew , Freitas-Junior Lucio , Charman Susan A. , Chatelain Eric
Published: April 2015

With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their
in vitro
activity against a panel of
Trypanosoma cruzi
strains;
in vivo
efficacy in a murine model of Chagas disease;
in vitro
toxicity and absorption, distribution, metabolism, and excretion characteristics; and
in vivo
pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture.
Anoxic Conditions Promote Species-Specific Mutualism between Gut Microbes
In Silico
Authors: Heinken Almut , Thiele Ines
Published: April 2015

The human gut is inhabited by thousands of microbial species, most of which are still uncharacterized. Gut microbes have adapted to each other's presence as well as to the host and engage in complex cross feeding. Constraint-based modeling has been successfully applied to predicting microbe-microbe interactions, such as commensalism, mutualism, and competition. Here, we apply a constraint-based approach to model pairwise interactions between 11 representative gut microbes. Microbe-microbe interactions were computationally modeled in conjunction with human small intestinal enterocytes, and the microbe pairs were subjected to three diets with various levels of carbohydrate, fat, and protein in normoxic or anoxic environments. Each microbe engaged in species-specific commensal, parasitic, mutualistic, or competitive interactions. For instance,
Streptococcus thermophilus
efficiently outcompeted microbes with which it was paired, in agreement with the domination of streptococci in the small intestinal microbiota. Under anoxic conditions, the probiotic organism
Lactobacillus plantarum
displayed mutualistic behavior toward six other species, which, surprisingly, were almost entirely abolished under normoxic conditions. This finding suggests that the anoxic conditions in the large intestine drive mutualistic cross feeding, leading to the evolvement of an ecosystem more complex than that of the small intestinal microbiota. Moreover, we predict that the presence of the small intestinal enterocyte induces competition over host-derived nutrients. The presented framework can readily be expanded to a larger gut microbial community. This modeling approach will be of great value for subsequent studies aiming to predict conditions favoring desirable microbes or suppressing pathogens.
Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron
Authors: Lammerts van Bueren Alicia , Saraf Aakanksha , Martens Eric C. , Dijkhuizen Lubbert
Published: April 2015

Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species
Bacteroides thetaiotaomicron
efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic
Lactobacillus reuteri
strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers.
B. thetaiotaomicron
metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (
sus
). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in
B. thetaiotaomicron
and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for
B. thetaiotaomicron
nutrient acquisition in the gastrointestinal tract.
Functional Analysis of Two
l
-Arabinose Transporters from Filamentous Fungi Reveals Promising Characteristics for Improved Pentose Utilization in Saccharomyces cerevisiae
Authors: Li Jingen , Xu Jing , Cai Pengli , Wang Bang , Ma Yanhe , Benz J. Philipp , Tian Chaoguang
Published: April 2015

Limited uptake is one of the bottlenecks for
l
-arabinose fermentation from lignocellulosic hydrolysates in engineered
Saccharomyces cerevisiae
. This study characterized two novel
l
-arabinose transporters, LAT-1 from
Neurospora crassa
and MtLAT-1 from
Myceliophthora thermophila
. Although the two proteins share high identity (about 83%), they display different substrate specificities. Sugar transport assays using the
S. cerevisiae
strain EBY.VW4000 indicated that LAT-1 accepts a broad substrate spectrum. In contrast, MtLAT-1 appeared much more specific for
l
-arabinose. Determination of the kinetic properties of both transporters revealed that the

K
m

values of LAT-1 and MtLAT-1 for
l
-arabinose were 58.12 ± 4.06 mM and 29.39 ± 3.60 mM, respectively, with corresponding
V
max
values of 116.7 ± 3.0 mmol/h/g dry cell weight (DCW) and 10.29 ± 0.35 mmol/h/g DCW, respectively. In addition, both transporters were found to use a proton-coupled symport mechanism and showed only partial inhibition by
d
-glucose during
l
-arabinose uptake. Moreover, LAT-1 and MtLAT-1 were expressed in the
S. cerevisiae
strain BSW2AP containing an
l
-arabinose metabolic pathway. Both recombinant strains exhibited much faster
l
-arabinose utilization, greater biomass accumulation, and higher ethanol production than the control strain. In conclusion, because of higher maximum velocities and reduced inhibition by
d
-glucose, the genes for the two characterized transporters are promising targets for improved
l
-arabinose utilization and fermentation in
S. cerevisiae
.
Bactericidal Compounds Controlling Growth of the Plant Pathogen Pseudomonas syringae pv. actinidiae, Which Forms Biofilms Composed of a Novel Exopolysaccharide
Authors: Ghods Shirin , Sims Ian M. , Moradali M. Fata , Rehm Bernd H. A.
Published: April 2015

Pseudomonas syringae
pv. actinidiae is the major cause of bacterial canker and is a severe threat to kiwifruit production worldwide. Many aspects of the disease caused by
P. syringae
pv. actinidiae, such as the pathogenicity-relevant formation of a biofilm composed of extracellular polymeric substances (EPSs), are still unknown. Here, a highly virulent strain of
P. syringae
pv. actinidiae, NZ V-13, was studied with respect to biofilm formation and architecture using a flow cell system combined with confocal laser scanning microscopy. The biofilm formed by
P. syringae
pv. actinidiae NZ V-13 was heterogeneous, consisting of a thin cellular base layer 5 μm thick and microcolonies with irregular structures. The major component of the EPSs produced by
P. syringae
pv. actinidiae NZ V-13 bacteria was isolated and identified to be an exopolysaccharide. Extensive compositional and structural analysis showed that rhamnose, fucose, and glucose were the major constituents, present at a ratio of 5:1.5:2. Experimental evidence that
P. syringae
pv. actinidiae NZ V-13 produces two polysaccharides, a branched α-
d
-rhamnan with side chains of terminal α-
d
-Fuc
f
and an α-
d
-1,4-linked glucan, was obtained. The susceptibility of the cells in biofilms to kasugamycin and chlorine dioxide was assessed. About 64 and 73% of
P. syringae
pv. actinidiae NZ V-13 cells in biofilms were killed when kasugamycin and chlorine dioxide were used at 5 and 10 ppm, respectively. Kasugamycin inhibited the attachment of
P. syringae
pv. actinidiae NZ V-13 to solid surfaces at concentrations of 80 and 100 ppm. Kasugamycin was bacteriostatic against
P. syringae
pv. actinidiae NZ V-13 growth in the planktonic mode, with the MIC being 40 to 60 ppm and a bactericidal effect being found at 100 ppm. Here we studied the formation, architecture, and composition of
P. syringae
pv. actinidiae biofilms as well as used the biofilm as a model to assess the efficacies of bactericidal compounds.
Nisin H Is a New Nisin Variant Produced by the Gut-Derived Strain Streptococcus hyointestinalis DPC6484
Authors: O'Connor Paula M. , O'Shea Eileen F. , Guinane Caitriona M. , O'Sullivan Orla , Cotter Paul D. , Ross R. Paul , Hill Colin
Published: April 2015

Accumulating evidence suggests that bacteriocin production represents a probiotic trait for intestinal strains to promote dominance, fight infection, and even signal the immune system. In this respect, in a previous study, we isolated from the porcine intestine a strain of
Streptococcus hyointestinalis
DPC6484 that displays antimicrobial activity against a wide range of Gram-positive bacteria and produces a bacteriocin with a mass of 3,453 Da. Interestingly, the strain was also found to be immune to a nisin-producing strain. Genome sequencing revealed the genetic determinants responsible for a novel version of nisin, designated nisin H, consisting of the
nshABTCPRKGEF
genes, with transposases encoded between
nshP
and
nshR
and between
nshK
and
nshG
. A similar gene cluster is also found in
S. hyointestinalis
LMG14581. Notably, the cluster lacks an equivalent of the nisin immunity gene,
nisI
. Nisin H is proposed to have the same structure as the prototypical nisin A but differs at 5 amino acid positions—Ile1Phe (i.e., at position 1, nisin A has Ile while nisin H has Phe), Leu6Met, Gly18Dhb (threonine dehydrated to dehydrobutyrine), Met21Tyr, and His31Lys—-and appears to represent an intermediate between the lactococcal nisin A and the streptococcal nisin U variant of nisin. Purified nisin H inhibits a wide range of Gram-positive bacteria, including staphylococci, streptococci,
Listeria
spp., bacilli, and enterococci. It represents the first example of a natural nisin variant produced by an intestinal isolate of streptococcal origin.
Chloride-Inducible Expression Vector for Delivery of Antimicrobial Peptides Targeting Antibiotic-Resistant Enterococcus faecium
Authors: Geldart Kathryn , Borrero Juan , Kaznessis Yiannis N.
Published: April 2015

Antibiotic-resistant enterococcal infections are a major concern in hospitals where patients with compromised immunity are readily infected.
Enterococcus faecium
bacteria are of particular interest as these pathogens account for over 80% of vancomycin-resistant enterococcal infections. Antimicrobial peptides (AMPs) produced at the site of infection by engineered bacteria may offer a potential alternative to traditional antibiotics for the treatment of resistant bacteria such as
E. faecium
. For this mode of delivery to be effective, it is essential to identify a suitable protein expression system that can be used in the desired delivery bacterium. In this study, we describe a promising chloride-inducible promoter and its application in the bacterial delivery of AMPs from
Lactococcus lactis
to reduce counts of
E. faecium
bacteria
in vitro
. Reporter gene studies show that at chloride concentrations found within the human intestines, the chloride-inducible promoter exhibits high levels of protein expression compared to those of the commonly used nisin-inducible promoter. These results indicate that this system is powerful and would not require the exogenous administration of an inducer molecule. In its application for AMP production against
E. faecium
in vitro
,
L. lactis
producing AMPs under the chloride promoter rapidly decreased
E. faecium
counts by nearly 10,000-fold. As an extension of this application, we also demonstrate the potential in using this type of delivery system in combination with traditional antibiotics to slow the development of resistance. Collectively, this study shows the promise of using a chloride-inducible promoter for the bacterial delivery of AMPs in the body for the treatment of vancomycin-resistant enterococci (VRE) and other antibiotic-resistant bacteria.