bluuebunny/crossref_metadata_2025 huggingface dataset:
SURFACE-INTERFACE MICROSTRUCTURES AND HIGH-TEMPERATURE WEAR PERFORMANCE OF HVOF-SPRAYED AND LASER-REMELTED NiCrBSi ALLOY COATINGS
Authors: KONG DEJUN , ZHAO BENGUO
Published: September 2016

A high-velocity oxygen fuel (HVOF)-sprayed NiCrBSi coating on H13 hot work die steel was processed with laser remelting; and the surface-interface morphologies, concentrations of chemical elements, and phases of the coating were analyzed with scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD), respectively. The friction-wear behaviors of the coating at high temperatures were investigated by the means of ball/plane contact. The effects of high temperature on the coefficient of friction (COF) and wear performance are discussed. The results show that the coating is dense and tightly bonded to the substrate at the interface. The average COFs at 500[Formula: see text]C, 600[Formula: see text]C, and 700[Formula: see text]C are 0.3749, 0.3609, and 0.4556, respectively. The wear mechanism is slight adhesive wear at 500[Formula: see text]C, and primarily oxidative wear and fatigue wear at 600[Formula: see text]C. The wear mechanism at 700[Formula: see text]C is oxidized wear and fatigue wear in the early stage, and mainly adhesive wear in the later stage. During high-temperature wear, an oxide film is formed on the coating surface, decreasing the wear resistance of the coating, which is primarily dependent on the compounds of Ni, Cr, B, Si, and C and the oxides of Si.
A first-principles study of the linear and nonlinear optical properties of isoxazole derivatives
Authors: Irfan Ahmad , Al-Sehemi Abdullah G. , Chaudhry Aijaz Rasool , Muhammad Shabbir
Published: September 2016

The isoxazole derivatives gained significant attention in our daily life from better biological activity to the semiconducting materials. This study deals in depth investigation of two isoxazole derivatives, i.e. 2-[(E)-(3,4-Dimethylisoxazol-5-yl)iminomethyl]phenol (1) and 1-[(E)-(3,4-Dimethylisoxazol-5-yl)iminomethyl]-2-naphthol (2) with respect to the geometric, charge transport, optoelectronic and nonlinear optical properties by density functional theory (DFT) and time-dependent DFT. The comprehensible intra-molecular charge transfer (ICT) was conceived from HOMOs to LUMOs. Strength of the electron donor groups was investigated on the absorption wavelengths, emission wavelengths, ionization potentials (IPs), electron affinities (EAs), total/partial densities of states and structure-property relationship. The smaller hole reorganization energies and superior transfer integrals of isoxazole derivatives (1 and 2) than the electron ones are leading to higher hole intrinsic mobility values as compared to the electron mobility exhibit that these systems would be good hole transport contenders. The first hyperpolarizability values are about 19 and 21 times larger than that of urea suggesting that 1 and 2 can also be considered as potential contestants for NLO applications as well.
A New Fast Numerical Method Based on Off-Step Discretization for Two-Dimensional Quasilinear Hyperbolic Partial Differential Equations
Authors: Mohanty R. K. , Khurana Gunjan
Published: September 2016

We report a new 3-level implicit compact numerical method of order four in time and four in space based on off-step discretization for the solution of two-space-dimensional quasilinear hyperbolic equation [Formula: see text], [Formula: see text], [Formula: see text] defined in the region [Formula: see text], [Formula: see text], [Formula: see text]. We require only 19 grid points for the unknown variable [Formula: see text] and two extra off-step points each in [Formula: see text]-, [Formula: see text]- and [Formula: see text]-directions. The proposed method is directly applicable to two-dimensional hyperbolic equations with singular coefficients, which is the main attraction of our work. We do not require any fictitious points for computation. The proposed method when applied to a two-dimensional damped wave equation is shown to be unconditionally stable. Operator splitting method is used to solve damped wave equation. Many benchmark problems are solved to confirm the fourth-order convergence of the proposed method.
Parallel Memory-Efficient Adaptive Mesh Refinement on Structured Triangular Meshes with Billions of Grid Cells
Authors: Meister Oliver , Rahnema Kaveh , Bader Michael
Published: September 2016

We present sam(oa)
2
, a software package for a dynamically adaptive, parallel solution of 2D partial differential equations on triangular grids created via newest vertex bisection. An element order imposed by the Sierpinski space-filling curve provides an algorithm for grid generation, refinement, and traversal that is inherently memory efficient. Based purely on stack and stream data structures, it completely avoids random memory access. Using an element-oriented data view suitable for local operators, concrete simulation scenarios are implemented based on control loops and event hooks, which hide the complexity of the underlying traversal scheme. Two case studies are presented: two-phase flow in heterogeneous porous media and tsunami wave propagation, demonstrated on the Tohoku tsunami 2011 in Japan.

sam(oa)
2
features hybrid MPI+OpenMP parallelization based on the Sierpinski order induced on the elements. Sections defined by contiguous grid cells define atomic tasks for OpenMP work sharing and stealing, as well as for migration of grid cells between MPI processes. Using optimized communication and load balancing algorithms, sam(oa)
2
achieves 88% strong scaling efficiency from 16 to 512 cores and 92% efficiency in a weak scaling test on 8,192 cores with 10 billion elements—all tests including adaptive mesh refinement and load balancing in each time step.
Short and Simple Cycle Separators in Planar Graphs
Authors: Fox-Epstein Eli , Mozes Shay , Phothilimthana Phitchaya Mangpo , Sommer Christian
Published: September 2016

We provide an implementation of an algorithm that, given a triangulated planar graph with
m
edges, returns a simple cycle that is a 3/4-balanced separator consisting of at most √8
m
edges. An efficient construction of a short and balanced separator that forms a simple cycle is essential in numerous planar graph algorithms, for example, for computing shortest paths, minimum cuts, or maximum flows. To the best of our knowledge, this is the first implementation of such a cycle separator algorithm with a worst-case guarantee on the cycle length.

We evaluate the performance of our algorithm and compare it to the planar separator algorithms recently studied by Holzer et al. [2009]. Out of these algorithms, only the Fundamental Cycle Separator (FCS) produces a simple cycle separator. However, FCS does not provide a worst-case size guarantee. We demonstrate that (1) our algorithm is competitive across all test cases in terms of running time, balance, and cycle length; (2) it provides worst-case guarantees on the cycle length, significantly outperforming FCS on some instances; and (3) it scales to large graphs.
Privacy-Preserving Publishing of Hierarchical Data
Authors: Ozalp Ismet , Gursoy Mehmet Emre , Nergiz Mehmet Ercan , Saygin Yucel
Published: September 2016

Many applications today rely on storage and management of semi-structured information, for example, XML databases and document-oriented databases. These data often have to be shared with untrusted third parties, which makes individuals’ privacy a fundamental problem. In this article, we propose anonymization techniques for privacy-preserving publishing of hierarchical data. We show that the problem of anonymizing hierarchical data poses unique challenges that cannot be readily solved by existing mechanisms. We extend two standards for privacy protection in tabular data (
k
-anonymity and ℓ-diversity) and apply them to hierarchical data. We present utility-aware algorithms that enforce these definitions of privacy using generalizations and suppressions of data values. To evaluate our algorithms and their heuristics, we experiment on synthetic and real datasets obtained from two universities. Our experiments show that we significantly outperform related methods that provide comparable privacy guarantees.
SecSIFT
Authors: Qin Zhan , Yan Jingbo , Ren Kui , Chen Chang Wen , Wang Cong
Published: September 2016

The image and multimedia data produced by individuals and enterprises is increasing every day. Motivated by the advances in cloud computing, there is a growing need to outsource such computational intensive image feature detection tasks to cloud for its economic computing resources and on-demand ubiquitous access. However, the concerns over the effective protection of private image and multimedia data when outsourcing it to cloud platform become the major barrier that impedes the further implementation of cloud computing techniques over massive amount of image and multimedia data. To address this fundamental challenge, we study the state-of-the-art image feature detection algorithms and focus on Scalar Invariant Feature Transform (SIFT), which is one of the most important local feature detection algorithms and has been broadly employed in different areas, including object recognition, image matching, robotic mapping, and so on. We analyze and model the privacy requirements in outsourcing SIFT computation and propose Secure Scalar Invariant Feature Transform (SecSIFT), a high-performance privacy-preserving SIFT feature detection system. In contrast to previous works, the proposed design is not restricted by the efficiency limitations of current homomorphic encryption scheme. In our design, we decompose and distribute the computation procedures of the original SIFT algorithm to a set of independent, co-operative cloud servers and keep the outsourced computation procedures as simple as possible to avoid utilizing a computationally expensive homomorphic encryption scheme. The proposed SecSIFT enables implementation with practical computation and communication complexity. Extensive experimental results demonstrate that SecSIFT performs comparably to original SIFT on image benchmarks while capable of preserving the privacy in an efficient way.
(Invited) Ecologically Friendly Recycling of Lithium-Ion Batteries - the LithoRec Process
Authors: Diekmann Jan , Hanisch Christian , Loellhoeffel Thomas , Schälicke Gerrit , Kwade Arno
Published: September 2016

Nowadays recycling processes for lithium-ion batteries focus on the recovery of nickel and cobalt. These processes are mainly pyro-metallurgical and as such energy and cost intensive. The project LithoRec, sponsored by the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB), aims at a realization of a new ecological recycling process tracing mechanical process-steps and considering recycling of lithium. This work presents the main challenges of the recycling of battery systems of electric and hybrid electric vehicles and the developed process chain, as well as the influence of a second crushing step on the yield and purity of the separated black mass containing the aged active materials.
First Lithiation/Delithiation Treatment on Agglomerated Nano-Si Particles Modified by Multi-Wall CNT and Its Characteristics
Authors: Ogisu Kenji , Yamane Kazuma , Hamai Kenta , Tagami Nobuyuki , Sasakawa Takako , Shiraki Masahito , Chiba Takatomi , Okazaki Noriyasu , Tada Akio
Published: September 2016

As for the anode materials of next generation Lithium Ion batteries, the silicon will be attractive one because of its large energy density, 3750-4200mAh/g. However the low first cycle efficiency and large volume change are major challenges to realize industrial application (1) (2). The objectives of this study are to improve the first cycle efficiency and to achieve less volume change (3) (4).We take an approach to find out a solution by adopting Nano-silicon particles modified by multi-wall CNT, agglomerated like a moss ball, and doing the first lithiation /delithiation to/from these particles directly in particulate form by electrolysis. The characteristics of these particles will be reported.
Probing the Aging Effects on Nanomechanical Properties of a Thin Film LiFePO4 Cathode
Authors: Demirocak Dervis Emre , Bhushan Bharat
Published: September 2016

Li-ion batteries offer great promise for future due to their superior gravimetric and volumetric energy density. One of the challenges is to improve the cycle life of Li-ion batteries which requires detailed understanding of the aging phenomenon. The aging mechanism of Li-ion batteries can have both chemical and mechanical origins. While the chemical degradation mechanisms have been studied extensively, mechanical degradation mechanisms have received little attention so far. In this study, we probed the changes in mechanical properties of a thin film and composite LiFePO4 cathode on pristine and aged samples. By studying both composite (active particles and binder) and thin film (active particles only) cathodes in parallel, it is possible to pinpoint the origin and magnitude of the mechanical degradation. Results showed that mechanical properties of the thin film LiFePO4 did not show as significant deterioration as in a composite LiFePO4 cathode indicating mechanical degradation in binder is more problematic than the mechanical degradation in the active material.
Semi-Empirical Modeling of Capacity Fade: A Practical Approach for Battery Pack Manufacturers
Authors: Wilke Stephen , Schweitzer Ben , Khateeb Siddique , Al-Hallaj Said
Published: September 2016

The growing demand for lithium ion batteries with long lifetime and warranty presents significant challenges for battery pack manufacturers to sufficiently understand cell ageing while keeping testing and validation costs low. To keep up with the rapid deployment of new cell types, appropriate modeling can be used to extrapolate limited-duration empirical results. We have implemented a semi-empirical modeling approach for predicting capacity fade under various operating conditions, using physics-based degradation mechanisms that provide a good fit to experimental data. Good agreement between the model and empirical results is demonstrated for two state-of-the-art 18650 cell types. The major improvement of this work over other approaches is that it minimizes the testing necessary to validate the unique capacity fade of each new cell type, allowing pack manufacturers to rapidly and accurately down-select the best candidate cells for specific applications.
Activated Lignin Based Carbon Nanofibers As Binder-Free Anodes for Lithium Ion Batteries
Authors: Stojanovska Elena , Serife Pampal Esra , Kilic Ali
Published: September 2016

In this study, activated carbon nanofibers were obtained from lignin/PVA blend. KOH was used as activating agent using two approaches. Scanning Electron Microscope and Raman spectroscopy were used for characterization of the morphology and structure of carbon nanofibers, while BET analysis was used to investigate their surface area and pore size distribution. Activated carbon nanofibers were used as free-standing anodes in a half cell Li-ion battery and their charge/discharge behavior was tested at different current densities. The results showed that the activated carbon nanofibers can increase the capacity and keep it stable.
Performance and Safety Characteristics of Si-Based Anode Materials for Li-Ion Batteries
Authors: Yanagida Masahiro , Mukai Takashi , Ikeuchi Yuuta , Sakamoto Taichi , Yamashita Naoto , Tanaka Hideaki
Published: September 2016

Silicon is one of promising active materials for Li-ion batteries for its high capacity. In order to utilize silicon-based materials as alternative anode, the composite electrodes were prepared from silicon-based materials with various binders. 1-Ah class laminated-type pouch cells were composed of the electrodes. To investigate the electrochemical properties of the silicon-based materials anode, an electrochemical test was conducted. From the view point of the safety characterization compared with electrode resistance, the results of nail insertion test for pouch cells were also carried out. In this study cycle performance was heavily dependent on the binder. The electrical conductivity of the Si electrodes resulted in different safety.
Processing of Aluminum-Doped Lithium Lanthanum Zirconate Garnet-Type Solid Electrolyte Materials
Authors: Fergus Jeffrey , Zhang Xingxing
Published: September 2016

Lithium lanthanum zirconate (LLZO) with the garnet crystal structure has high lithium ion conductivity and good electrochemical stability, so it is an attractive material for use as the solid electrolyte in lithium ion batteries. One of the challenges in the application of LLZO is processing the material to obtain the desired composition, crystal structure and morphology. In this paper, results on processing of LLZO materials for use in single-phase and composite solid electrolyte materials are presented.
Ionic Liquid Based Polymer Gel Electrolyte Membranes for Lithium Ion Rechargeable Batteries
Authors: Kataria Shalu - , Balo Liton , Gupta Himani , Singh Varun Kumar , Singh Shishir Kumar , Tripathi Alok Kumar , Verma Yogendra Lal , Singh Rajendra Kumar
Published: September 2016

Li-ion conducting polymeric membranes containing 1-butyl-3-methylimidazolium tetrafluroborate (BMIMBF4), polymer poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP), and Lithium bis(trifluoromethanesulfonyl)imide) (LiTFSI) salt have been synthesized and characterized by various techniques. The synthesized polymeric membrane have good free-standing characteristics, good thermal stability (300-400 oC) and also have a wide electrochemical window (ECW) ~ 4.0 to 4.50V. The room temperature ionic conductivity of the membrane (PVdF-HFP+20 wt.% LiTFSI) + 60% BMIMBF4 was found to be 1.7mS.cm-1.
Electrochemical and Chemical Na+/Li+ Ion Exchange in Na-Based Cathode Materials
Authors: Kosova Nina V. , Tsapina Anna M. , Petrov Sergey A. , Slobodyuk Arseny B.
Published: September 2016

Na2FeP2O7 sodium iron pyrophosphate with a triclinic symmetry (the space group P-1) has been prepared by mechanochemically assisted solid state synthesis. Electrochemical performance of the pristine Na2FeP2O7, NaFeP2O7 prepared by chemical oxidation with NO2BF4 and NaLiFeP2O7 obtained by non-oxidative Na+/Li+ ion exchange with LiBr were studied by galvanostatic cycling in a Li cell with Li as an anode and LiPF6 dissolved in EC+DMC as an electrolyte. XRD, EDX, Mössbauer and NMR spectroscopy studies showed that all the samples were active upon cycling in Li cells which resulted in exchange of one ~Na+ for one Li+ per f.u. to produce a new mixed phase NaLiFeP2O7 with the same triclinic structure as Na2FeP2O7 and good electrochemical performance.
Inhomogeneities in Large Format Lithium Ion Cells: A Study by Battery Modelling Approach
Authors: Arunachala Raghavendra , Parthasarathy Chethan , Jossen Andreas , Garche Juergen
Published: September 2016

The performance of lithium ion battery cells is influenced besides the cell chemistry, also by microscopic and macroscopic parameters. In short format cells, the macroscopic variables such as cell geometry, aspect ratio, material thickness, tab configuration etc. do not significantly affect current, voltage, state of charge (SOC) and temperature distribution. However, they cannot be neglected as the cell size increases, especially in large format cells, where the distributions becomes non homogeneous. These inhomogeneities adversely affect the cell’s performance and a long exposure leads to localized aging. This paper presents a spatially resolved modelling technique in Matlab/Simulink to evaluate cell inhomogeneity. It compares current, voltage and SOC distribution of 8 Ah and 75 Ah cells and how the distribution changes from a fresh cell to its end of life (EOL).
New Formulations of High-Voltage Cathodes for Li-Ion Batteries with Water-Processable Binders
Authors: Bigoni Francesca , De Giorgio Francesca , Soavi Francesca , Arbizzani Catia
Published: September 2016

The use of water-processable binders could lower production costs and grant easier and more environment-friendly production of Li-ion batteries. This work investigates the use of two water-processable binders, namely polyvinylacetate (PVA) and sodium alginate (Alg), in high-voltage cathode electrodes for Li-ion batteries. We focused our work on the use of these sustainable binders for cathodes based on LiNi0.5Mn1.5O4, a commercially available material with a very high Li+ deinsertion/insertion potential (4.7-4.75 V versus Li+/Li) and a theoretical specific capacity of 147 mAh g-1. The electrochemical performance of cathodes with PVA and Alg are compared to those obtained with PVdF-based electrodes at 30°C in conventional electrolyte. Among all, Alg-based cathodes show the best rate capability up to 5C and cycle stability, with 95% capacity retention after 100 cycles because of the formation of thinner and less resistive layer on the electrode than PVA- and PVdF-based cathodes.
Silyl and Silyl/Carbonate Blend Electrolytes for Lithium-Ion Battery Applications
Authors: Lyons Leslie J. , Peña Hueso Adrián , Johnson Tobias , West Robert
Published: September 2016

Silyl glycol molecules and silyl nitrile molecules were used to prepare electrolytes with the salts LiPF6 and LiTFSI, Ionic conductivities of silyl electrolytes at 298 K range from 1.0 to 2.3 mScm-1 for salt concentrations at 1 M. Ionic conductivities of the silyl solvent/carbonate blend electrolytes increase, achieving ionic conductivities at 298 K of 5-6 mScm-1. From PFG-STE NMR experiments we find higher lithium transference numbers in silyl electrolytes than those in analogous cyclic carbonate electrolytes. The lithium transference numbers increase with increasing temperature for PF6
- electrolytes while those based on TFSI- electrolytes decrease with increasing temperature. From both the ionic conductivity and NMR diffusion measurements, we have calculated the extent of ion dissociation in these electrolytes. Ion dissociation generally decreases with increasing temperature from 300-330 K.
Lithiated Polyacrylic Acid Binder to Enhance the High Rate and Pulse Charge Performances in Graphite Anodes
Authors: Chiu Kuo-Feng , Leu Hoang-Jyh , Su Shih-Hsuan , Wu Rong-Zong
Published: September 2016

Polyacrylic acid (PAA) was used as a water-soluble binder for graphite anodes in lithium-ion batteries and polyvinylidene fluoride (PVdF) binder were also prepared. The PAA based binders were lithiated by titration using aqueous LiOH (Li-PAA) and controlled by adjusting the pH of the solution. The graphite anodes containing the optimized Li-PAA binder showed greatly improved high-rate capability. These results can be attributed to the increase of Li+-ion concentrations in the active materials vicinity, which reduces the charge transfer resistance. To test the durability under the conditions of a green-energy grid, all samples were charged at 0.2C rate, and during each period of the charge process 50 current pulses were applied. The pulse current was 5C. It was found that electrode containing Li-PAA with higher Li+-ion concentrations exhibit higher durability than the conventional anodes. Our results indicate that Li-PAA is a suitable binder for Li-ion battery anodes in green-energy grid applications.
Analytical Charged Capacity Expression of Lithium-Ion Battery for SOH Estimation Based on Constant Current Charging Curves
Authors: Li Xue , Jiang Jiuchun , Ju Qun , Chen Zonghai , Zhang Zhengcheng , Zhang Caiping
Published: September 2016

Accurate evaluation of the state of health (SOH) plays an important role in battery management systems. The incremental capacity (IC) analysis method is applied to analyze battery aging mechanisms and estimate SOH. The charged capacity can be obtained by integration of the IC curve. To obtain the analytical charged capacity expression based on the IC curve, the fitting results of the IC curve by Gaussian functions and Lorentz functions are compared. The comparison results show that the Lorentz functions are more suitable than Gaussian functions on fitting IC curve and estimating charged capacity because of its relatively simpler integration form. Therefore, the analytical charged capacity equation is proposed by the integration of the Lorentz functions. The experimental results demonstrate that the capacity estimation error is lower than 1.5%.
Development of Large Format NMC-Graphite Lithium Ion Pouch Cell with Aqueous Processed Electrodes
Authors: Kvasha Andriy , Urdampilleta Idoia , De Meatza Iratxe , Colombo Roberta , Ulmann Pirmin , Gulas Michal , Gutierrez Cesar , Bengoechea Miguel , Blazquez Jose Alberto , Miguel Oscar , Grande Hans-Jurgen
Published: September 2016

The development of a large format LiNi0.33Mn0.33Co0.33O2 (NMC) - Graphite pouch cell with both electrodes prepared using waterborne PVdF binders is reported. The formulations and design of the positive and negative electrodes have been optimized to meet the MAT4BAT EU project objectives. The negative and positive electrode slurries with elaborated formulations have been scaled up effectively to kilogram scale and ~100 meters length double-side coated electrodes have been manufactured. Finally, an NMC-Graphite pouch cell with nominal capacity 17 Ah demonstrated promising C-rate capability and long term cyclability reaching 80% of initial discharge capacity after 3,200 cycles with 100% depth of discharge.
Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach
Authors: Shaylor Lara A. , Hwang Sung Jin , Sanders Kenton M. , Ward Sean M.
Published: September 2016

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase ( Nos1 −/−) and P2Y1 receptors ( P2ry1 −/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 −/− mice IJPs and relaxations persisted whereas in P2ry1 −/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species.
Statins improve NASH via inhibition of RhoA and Ras
Authors: Schierwagen Robert , Maybüchen Lara , Hittatiya Kanishka , Klein Sabine , Uschner Frank E. , Braga Tarcio T. , Franklin Bernardo S. , Nickenig Georg , Strassburg Christian P. , Plat Jogchum , Sauerbruch Tilman , Latz Eicke , Lütjohann Dieter , Zimmer Sebastian , Trebicka Jonel
Published: September 2016

Nonalcoholic steatohepatitis (NASH), especially as part of the metabolic syndrome (MS), is an increasing burden in Western countries. Statins are already used in MS and seem to be beneficial in liver diseases. The aim of this study was to investigate the molecular mechanisms underlying pleiotropic effects on small GTPases of statins in NASH. NASH within MS was induced in 12-wk-old apoE−/− mice after 7 wk of Western diet (NASH mice). Small GTPases were inhibited by activated simvastatin (SMV), NSC23766 (NSC), or Clostridium sordellii lethal toxin (LT) by using subcutaneous osmotic minipumps. Hepatic steatosis, inflammation, and fibrosis were assessed by histology, Western blot, and RT-PCR measurements of cholesterol and hydroxyproline content. SMV treatment significantly decreased hepatic inflammation and fibrosis, but had no significant effect on steatosis and hepatic cholesterol content in NASH. SMV blunted fibrosis due to inhibition of both RhoA/Rho kinase and Ras/ERK pathways. Interestingly, inhibition of RAC1 and Ras (by LT) failed to decrease fibrosis to the same extent. Inhibition of RAC1 (by NSC) showed no significant effect at all. Inhibition of RhoA and Ras downstream signaling by statins is responsible for the beneficial hepatic effects in NASH.
Lactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium
Authors: Kumar Anoop , Anbazhagan Arivarasu N. , Coffing Hayley , Chatterjee Ishita , Priyamvada Shubha , Gujral Tarunmeet , Saksena Seema , Gill Ravinder K. , Alrefai Waddah A. , Borthakur Alip , Dudeja Pradeep K.
Published: September 2016

Impaired absorption of electrolytes is a hallmark of diarrhea associated with inflammation or enteric infections. Intestinal epithelial luminal membrane NHE3 (Na+/H+ exchanger 3) and DRA (Down-Regulated in Adenoma; Cl−/HCO3− exchanger) play key roles in mediating electroneutral NaCl absorption. We have previously shown decreased NHE3 and DRA function in response to short-term infection with enteropathogenic E. coli (EPEC), a diarrheal pathogen. Recent studies have also shown substantial downregulation of DRA expression in a diarrheal model of infection with Citrobacter rodentium, the mouse counterpart of EPEC. Since our previous studies showed that the probiotic Lactobacillus acidophilus (LA) increased DRA and NHE3 function and expression and conferred protective effects in experimental colitis, we sought to evaluate the efficacy of LA in counteracting NHE3 and DRA inhibition and ameliorating diarrhea in a model of C. rodentium infection. FVB/N mice challenged with C. rodentium [1 × 109 colony-forming units (CFU)] with or without administration of live LA (3 × 109 CFU) were assessed for NHE3 and DRA mRNA and protein expression, mRNA levels of carbonic anhydrase, diarrheal phenotype (assessed by colonic weight-to-length ratio), myeloperoxidase activity, and proinflammatory cytokines. LA counteracted C. rodentium-induced inhibition of colonic DRA, NHE3, and carbonic anhydrase I and IV expression and attenuated diarrheal phenotype and MPO activity. Furthermore, LA completely blocked C. rodentium induction of IL-1β, IFN-γ, and CXCL1 mRNA and C. rodentium-induced STAT3 phosphorylation. In conclusion, our data provide mechanistic insights into antidiarrheal effects of LA in a model of infectious diarrhea and colitis.
Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus
Authors: Lang Ivan M. , Medda Bidyut K. , Jadcherla Sudarshan R. , Shaker Reza
Published: September 2016

Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of the EPSR was related to the position, magnitude, and length of the stimulus in the esophagus. The most effective stimulus was long, strong, and situated in the cervical esophagus. Acidification of the esophagus activated pharyngeal swallows and sensitized the receptors that activate the EPSR. The EPSR was blocked by local anesthesia applied to the esophageal lumen, and electrical stimulation of the recurrent laryngeal nerve caudal to the cricoid cartilage (RLNc) activated the pharyngeal swallow response. We conclude that the EPSR is activated in a probabilistic manner. The receptors mediating the EPSR are probably mucosal slowly adapting tension receptors. The sensory neural pathway includes the RLNc and superior laryngeal nerve. We hypothesize that, because the EPSR is observed in human infants and animals, but not human adults, activation of EPSR is related to the elevated position of the larynx. In this situation, the EPSR occurs rather than secondary peristalsis to prevent supraesophageal reflux when the esophageal bolus is in the proximal esophagus.
Changes in cardiac Nav1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors
Authors: Xu Qin , Patel Dakshesh , Zhang Xian , Veenstra Richard D.
Published: September 2016

Histone deacetylase (HDAC) inhibitors are small molecule anticancer therapeutics that exhibit limiting cardiotoxicities including QT interval prolongation and life-threatening cardiac arrhythmias. Because the molecular mechanisms for HDAC inhibitor-induced cardiotoxicity are poorly understood, we performed whole cell patch voltage-clamp experiments to measure cardiac sodium currents ( INa) from wild-type neonatal mouse ventricular or human-induced pluripotent stem cell-derived cardiomyocytes treated with trichostatin A (TSA), vorinostat (VOR), or romidepsin (FK228). All three pan-HDAC inhibitors dose dependently decreased peak INa density and shifted the voltage activation curve 3- to 8-mV positive. Increases in late INa were not observed despite a moderate slowing of the inactivation rate at low activating potentials (<−40 mV). Scn5a mRNA levels were not significantly altered but NaV1.5 protein levels were significantly reduced. Immunoprecipitation with anti-NaV1.5 and Western blotting with anti-acetyl-lysine antibodies indicated that NaV1.5 acetylation is increased in vivo after HDAC inhibition. FK228 inhibited total cardiac HDAC activity with two apparent IC50s of 5 nM and 1.75 μM, consistent with previous findings with TSA and VOR. FK228 also decreased ventricular gap junction conductance ( gj), again consistent with previous findings. We conclude that pan-HDAC inhibition reduces cardiac INa density and NaV1.5 protein levels without affecting late INa amplitude and, thus, probably does not contribute to the reported QT interval prolongation and arrhythmias associated with pan-HDAC inhibitor therapies. Conversely, reductions in gj may enhance the occurrence of triggered activity by limiting electrotonic inhibition and, combined with reduced INa, slow myocardial conduction and increase vulnerability to reentrant arrhythmias.
Activation of heat shock response augments fibroblast growth factor-1 expression in wounded lung epithelium
Authors: Scheraga Rachel G. , Thompson Christopher , Tulapurkar Mohan E. , Nagarsekar Ashish C. , Cowan Mark , Potla Ratnakar , Sun Junfeng , Cai Rongman , Logun Carolea , Shelhamer James , Todd Nevins W. , Singh Ishwar S. , Luzina Irina G. , Atamas Sergei P. , Hasday Jeffrey D.
Published: September 2016

We previously showed that coincident exposure to heat shock (HS; 42°C for 2 h) and TNF-α synergistically induces apoptosis in mouse lung epithelium. We extended this work by analyzing HS effects on human lung epithelial responses to clinically relevant injury. Cotreatment with TNF-α and HS induced little caspase-3 and poly(ADP-ribose) polymerase cleavage in human small airway epithelial cells, A549 cells, and BEAS2B cells. Scratch wound closure rates almost doubled when A549 and BEAS2B cells and air-liquid interface cultures of human bronchial epithelial cells were heat shocked immediately after wounding. Microarray, qRT-PCR, and immunoblotting showed fibroblast growth factor 1 (FGF1) to be synergistically induced by HS and wounding. Enhanced FGF1 expression in HS/wounded A549 was blocked by inhibitors of p38 MAPK (SB203580) or HS factor (HSF)-1 (KNK-437) and in HSF1 knockout BEAS2B cells. PCR demonstrated FGF1 to be expressed from the two most distal promoters in wounded/HS cells. Wound closure in HS A549 and BEAS2B cells was reduced by FGF receptor-1/3 inhibition (SU-5402) or FGF1 depletion. Exogenous FGF1 accelerated A549 wound closure in the absence but not presence of HS. In the presence of exogenous FGF1, HS slowed wound closure, suggesting that it increases FGF1 expression but impairs FGF1-stimulated wound closure. Frozen sections from normal and idiopathic pulmonary fibrosis (IPF) lung were analyzed for FGF1 and HSP70 by immunofluorescence confocal microscopy and qRT-PCR. FGF1 and HSP70 mRNA levels were 7.5- and 5.9-fold higher in IPF than normal lung, and the proteins colocalized to fibroblastic foci in IPF lung. We conclude that HS signaling may have an important impact on gene expression contributing to lung injury, healing, and fibrosis.
Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury
Authors: Zhao Jiping , Yu Hao , Liu Yudong , Gibson Sara A. , Yan Zhaoqi , Xu Xin , Gaggar Amit , Li Pui-Kai , Li Chenglong , Wei Shi , Benveniste Etty N. , Qin Hongwei
Published: September 2016

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with high mortality. Macrophages and neutrophils are responsible for inflammatory responses in ALI and ARDS, which are characterized by excessive production of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma. Aberrant activation of the JAK/STAT pathway is critical for persistent inflammation in many conditions such as infection and autoimmunity. Given the importance of the STAT3 transcription factor in activating macrophages and neutrophils and augmenting inflammation, we investigated the therapeutic potential of inhibiting STAT3 activity using the small-molecule STAT3 inhibitor, LLL12. Our results demonstrate that LPS induces STAT3 activation in macrophages in vitro and in CD45+CD11b+ cells from BALF in the LPS-induced ALI model in vivo. LLL12 treatment inhibits LPS-induced lung inflammation in the ALI model, which is accompanied by suppression of LPS-induced STAT3 activation and an inhibition of macrophage and inflammatory cell infiltration in lung and BALF. LLL12 treatment also suppresses expression of proinflammatory genes including IL-1β, IL-6, TNF-α, iNOS, CCL2, and MHC class II in macrophages and inflammatory cells from BALF and serum as determined by ELISA. Furthermore, hyperactivation of STAT3 in LysMCre-SOCS3fl/fl mice accelerates the severity of inflammation in the ALI model. Both pre- and post-LPS treatment with LLL12 decrease LPS-induced inflammatory responses in mice with ALI. Importantly, LLL12 treatment attenuates STAT3 phosphorylation in human peripheral blood mononuclear cells induced by plasma from patients with ARDS, which suggests the feasibility of targeting the STAT3 pathway therapeutically for patients with ALI and ARDS.
Postinjury biomechanics of Achilles tendon vary by sex and hormone status
Authors: Fryhofer George W. , Freedman Benjamin R. , Hillin Cody D. , Salka Nabeel S. , Pardes Adam M. , Weiss Stephanie N. , Farber Daniel C. , Soslowsky Louis J.
Published: September 2016

Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats ( n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing.
Effect of alterations in blood volume with bed rest on glucose tolerance
Authors: Dandanell S. , Oberholzer L. , Keiser S. , Andersen A. B. , Haider T. , Hilty M. P. , Meinild-Lundby A. K. , Lundby C.
Published: September 2016

Bed rest leads to rapid impairments in glucose tolerance. Plasma volume and thus dilution space for glucose are also reduced with bed rest, but the potential influence on glucose tolerance has not been investigated. Accordingly, the aim was to investigate whether bed rest-induced impairments in glucose tolerance are related to a concomitant reduction in plasma volume. This hypothesis was tested mechanistically by restoring plasma volume with albumin infusion after bed rest and parallel determination of glucose tolerance. Fifteen healthy volunteers (age 24 ± 3 yr, body mass index 23 ± 2 kg/m2, maximal oxygen uptake 44 ± 8 ml·min−1·kg−1; means ± SD) completed 4 days of strict bed rest. Glucose tolerance [oral glucose tolerance test (OGTT)] and plasma and blood volumes (carbon monoxide rebreathing) were assessed before and after 3 days of bed rest. On the fourth day of bed rest, plasma volume was restored by means of an albumin infusion prior to an OGTT. Plasma volume was reduced by 9.9 ± 3.0% on bed rest day 3 and area under the curve for OGTT was augmented by 55 ± 67%. However, no association ( R2= 0.09, P = 0.33) between these simultaneously occurring responses was found. While normalization of plasma volume by matched albumin administration (408 ± 104 ml) transiently decreased ( P < 0.05) resting plasma glucose concentration (5.0 ± 0.4 to 4.8 ± 0.3 mmol/l), this did not restore glucose tolerance. Bed rest-induced alterations in dilution space may influence resting glucose values but do not affect area under the curve for OGTT.
The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial Pathology Tissue Resource
Authors: Zhu Claire S. , Huang Wen-Yi , Pinsky Paul F. , Berg Christine D. , Sherman Mark , Yu Kelly J. , Carrick Danielle M. , Black Amanda , Hoover Robert , Lenz Petra , Williams Craig , Hawkins Laura , Chaloux Matthew , Yurgalevitch Susan , Mathew Sunitha , Miller Amy , Olivo Vanessa , Khan Asia , Pretzel Shannon M. , Multerer Deborah , Beckmann Patricia , Broski Karen G. , Freedman Neal D.
Published: September 2016

Background: Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial.

Methods: Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction.

Results: Pathology tissue specimens were obtained for prostate cancer (n = 1,052), lung cancer (n = 434), colorectal cancer (n = 675) and adenoma (n = 658), ovarian cancer and borderline tumors (n = 212), breast cancer (n = 870), and bladder cancer (n= 204). The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories.

Conclusions: Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis.

Impact: The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25(12); 1635–42. ©2016 AACR.
Quality Assurance in Biobanking for Pre-Clinical Research
Authors: Simeon-Dubach Daniel , Zeisberger Steffen M. , Hoerstrup Simon P.
Published: September 2016

It is estimated that not less than USD 28 billion are spent each year in the USA alone on irreproducible pre-clinical research, which is not only a fundamental loss of investment and resources but also a strong inhibitor of efficiency for upstream processes regarding the translation towards clinical applications and therapies. The issues and cost of irreproducibility has mainly been published on pre-clinical research. In contrast to pre-clinical research, test material is often being transferred into humans in clinical research. To protect treated human subjects and guarantee a defined quality standard in the field of clinical research, the manufacturing and processing infrastructures have to strictly follow and adhere to certain (inter-)national quality standards. It is assumed and suggested by the authors that by an implementation of certain quality standards within the area of pre-clinical research, billions of USD might be saved and the translation phase of promising pre-clinical results towards clinical applications may substantially be improved. In this review, we discuss how an implementation of a quality assurance (QA) management system might positively improve sample quality and sustainability within pre-clinically focused biobank infrastructures. Biobanks are frequently positioned at the very beginning of the biomedical research value chain, and, since almost every research material has been stored in a biobank during the investigated life cycle, biobanking seems to be of substantial importance from this perspective. The role model of a QA-regulated biobank structure can be found in biobanks within the context of clinical research organizations such as in regenerative medicine clusters.