bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic comparison of oral tablet and suspension formulations of grapiprant, a novel therapeutic for the pain and inflammation of osteoarthritis in dogs
Authors: Rausch‐Derra L. C. , Rhodes L. , Freshwater L. , Hawks R.
Published: March 2016

A new anti‐inflammatory drug for pain (grapiprant) was recently shown to have minimal side effects following chronic (9‐month) daily oral dose of 6 or 50 mg/kg suspension. The current study compares the pharmacokinetics of the formulation used in the chronic safety study to those of the tablet formulation that will be marketed upon FDA approval. Sixteen Beagle dogs were randomized to receive single doses of either 6 or 50 mg/kg grapiprant as both suspension and table formulations within a cross‐over design with a 15‐day washout. Clinical observations were vomiting in one high‐dose suspension dog and loose stools in two dogs, one in each 6 mg/kg formulation group. For both formulations, grapiprant reached a maximum concentration within two hours. The tablet formulation had better bioavailability, with AUClast values 34% higher at 6 mg/kg and 64% higher at 50 mg/kg compared to the suspension. Results on Day 0 were similar to those reported on Day 15, suggesting little to no accumulation. Using conversion factors of 1.34 and 1.64, these findings suggest that the 6 and 50 mg/kg suspension doses are equivalent to 4.5 and 30 mg/kg tableted doses, respectively. Combining these findings with the 9‐month safety study demonstrates that safety was evaluated at doses approximately 15‐fold above the demonstrated therapeutic dose of 2 mg/kg and 10‐fold over the ‘safety dose’, defined as the maximum dose a dog of any body weight could receive when dosed at 2 mg/kg with whole or half‐tablets.
Primula persimilis sp. nov. (Primulaceae) from Sichuan, China
Authors: Xu Yuan , Yan Hai‐Fei , Hu Chi‐Ming , Hao Gang
Published: March 2016

A new species of Primulaceae, Primula persimilis G. Hao, C.M. Hu & Y. Xu, from Sichuan, China, is described and illustrated. In general morphology it is allied to the species of P. sect. Monocarpicae, characterized by the presence of multi‐cellular hairs, the distinctly petiolate leaves, a campanulate calyx, and a globose or cylindrical capsule with valvate dehiscence. The new species superficially resembles P. tsiangii W.W. Smith, but can be distinguished by its white flowers, longer calyx lobes, and cylindrical capsules.
Non‐residents’ Holdings, Market Volatility and Public Debt Sustainability. An Analysis with Data for Italy
Authors: Cafiso Gianluca
Published: March 2016

Non‐residents’ holdings (NRH) of debt securities have been large in euro area countries, but during the euro area debt crisis some of those countries experienced a steep contraction of such holdings. The analysis aims to provide a data‐founded explanation of what is behind the decrease observed in 2011 by testing two alternative hypotheses. At the same time, we discuss how that decrease might have endangered the sustainability of public debt and study the empirical relevance of the most important of those processes. The topics presented refer to any advanced economy, but we check the hypotheses discussed by taking Italy as a case study because of data constraints. Italy is an interesting country to consider since it is a very large debt issuer. Our results point towards the importance of market volatility to explain variations of NRH, but those holdings do not seem to influence debt sustainability.
CHARACTERISATION AND MODELLING OF PEDESTRIAN FLOWS IN HOSPITAL AND ACADEMIC ENVIRONMENTS
Authors: Alhassan Hashim Mohammed , Mashros Nordiana
Published: March 2016

This paper examined pedestrian characteristics in two urban facilities namely a teaching hospital and a university campus. The aim was to determine if pedestrian flow features in these facilities differed from those in downtown areas. The objectives were to measure pedestrian flow rates and model their walking behaviour. Eleven sites located within these facilities were selected for study. The results indicated that the male walked faster than the female in the university campus while the female was faster in the hospital environment. Also the university campus saw more groups of pedestrians in the traffic mix than was the case in the hospital environment where 93% of the pedestrians were in single files. The male walked faster than the female by 7% in the university environment while the female were faster by 4% in the hospital environment. The modelling effort showed that the free walking speed in the university environment was 68.052 m/min with a critical density of 3.15 ped/m2. That of the hospital environment was 75.099 m/min and a critical density of 4.36 ped/m2. Since the speed-density relationships for the two facilities revealed a highly randomized plot, the data was fit to the normal distribution and pdf and cdf were used to assess the quality of the flow.  For the university environment the results showed that 15% of the combined pedestrians walked below 56.88 m/min while 50% of the pedestrians walked below 66.67m/min and 85% walked below 72.50 m/min. Similarly, the results of the hospital environment showed that 15th percentile of the combined pedestrians walked below 69.75 m/min. The median speed of pedestrians was 72.50 m/min while 85% of the pedestrians walked below 75.25 m/min.  In both cases, the 15 percentile speeds were 14% and 18.5% less than the median speeds in both facilities respectively. Thus flow breakdowns are unexpected in the two facilities.
ANALYSIS OF CAR FOLLOWING HEADWAY ALONG MULTILANE HIGHWAY
Authors: Sanik Mohd Erwan , Prasetijo Joewono , Mat Nor Ahmad Hakimi , Hamid Nor Baizura , Yusof Ismail , Jaya Ramadhansyah Putra
Published: March 2016

This study describes driver’s car following headway on multilane highways.  The aim of this study is to analyse the driver’s car following headway along multilane highway at four selected locations.  The objectives of this study were to determine car headway at Jalan Batu Pahat – Ayer Hitam multilane highway and to develop linear regression models to present the relationships between headway and speed.  Videotaping method was used in field data collection during peak hours.  Data were extracted from recorded video by using the image processing technique software.  The distance headways and associated vehicles speeds were classified into vehicle following category by vehicle type: car following car, car following heavy goods vehicle, heavy goods vehicle following heavy goods vehicle and heavy goods vehicle following car categories.  Linear regressions models were used to develop the relationships between headway and speed. Based on all headway distribution, it is found that patterns of the vehicle headways at four study locations were similar, which shown a significant number of the vehicles travel at headways less than 5 seconds.  Furthermore, it can be concluded that many drivers tend to follow the vehicles ahead closely on multilane highways.  The regression models were significantly reliable based on their R-square values which are ranging between 0.80 and 0.95.  From the analysis, cars were found to maintain larger headways when following heavy goods vehicles compare to when following other cars.
EXPLORATORY STUDY ON AIRBAG SUITABILITY FOR LOW ENGINE CAPACITY MOTORCYCLES
Authors: Ariffin Aqbal Hafeez , Solah Mohd Syazwan , Hamzah Azhar , Md Isa Mohd Hafzi , Mohd Jawi Zulhaidi , Md Yusoff Nur Izzi , Hainin Mohd Rosli
Published: March 2016

Motorcyclist constituted more than 50% of road deaths in Malaysia. Statistics showed that most fatal motorcyclist crashes involved passenger cars: with sideswipe or side impact reported to be the most frequent crash configurations. Many related studies have been performed to completely understand such motorcycle crashes which resulted in many safety inventions. These include installation of airbag onto motorcycle to study its effectiveness in potentially reducing motorcyclist’s injury. However, previous related studies known mainly dealt airbag’s effectiveness for large cc motorcycles. Hence, an exploratory study was conducted to study airbag’s suitability in mitigating rider’s injury during collision for motorcycle with low engine capacity (cc). Two different full-scale crash tests of motorcycle (with and without mounted airbag) side-impacting passenger car were conducted in accordance to ISO 13232. The test results in terms of high-speed video recordings (crash kinematics), motorcycle damage profiles and dummy injuries were analysed and discussed. It could be suggested from the results obtained that an airbag system for low cc motorcycle is feasible and further study is needed for better airbag concept and design which could reduce motorcyclist injury during collision.
BUSINESS HOURS VS NON-BUSINESS HOURS IN BUSINESS ZONE : IMPACT ON SPEED AND ACCELERATION
Authors: Rohani M.M. , Daniel B.D. , Aman M.Y. , Prasetijo J. , Mustafa A.A. , Rahman R.
Published: March 2016

The main purpose of this study is to assess the impact of business and non-business hours on speed and acceleration of car drivers. Driving profiles from 40 drivers were gathered on site using Global Positioning System (GPS) device during both business and non-business hours. Comparison tests conducted found that during business hours, drivers drove significantly slower than non-business hours. The descriptive analysis conducted also shows that drivers applied 30% higher acceleration during non-business hours. Results from this study confirm that business hours have an impact on the variation of speed and acceleration in business zone areas.
EVALUATING THE COOLING RATE OF HOT MIX ASPHALT IN TROPICAL CLIMATE
Authors: Hashim Wardati , Hainin Mohd Rosli , Ismail Norfarah Nadia , Md. Yusoff Nur Izzi , Abdullah Mohd Ezree , Abdul Hassan Norhidayah
Published: March 2016

This paper aims to investigate the environmental effect on cooling rate and to determine the appropriate time available for compaction (TAC) using laboratory tests. This includes the study parameters, namely solar flux, base and ambient temperatures (daytime and night-time paving) and wind velocity, focusing on hot mix asphalt (HMA) asphalt concrete wearing with 14 mm nominal maximum aggregate size (ACW14) mix type for the wearing course and ACB28 mix type for the binder course. Samples were prepared in slab moulds 30.5 cm × 30.5 cm × 5 cm and compacted using a manually operated steel-roller. Readings were taken by averaging the temperature measurements at the middle and surface of the slabs and a temperature of 160 ºC was used as the mixing temperature. A control sample was prepared for each mix type and tested in the laboratory without the influence of wind velocity and solar flux. It was found that the cooling rate of HMA is significantly affected by environmental factors, thus influencing the TAC. The TAC tends to decrease by 15-50% during windy and night conditions but increases by up to 100% during daytime conditions compared to the control samples.
A REVIEW ON APPLICATION OF WASTE COOKING OIL AS REJUVENATOR IN POROUS ASPHALT MIXTURE
Authors: Wan Azahar Wan Nur Aifa , Bujang Mastura , Jaya Ramadhansyah Putra , Hainin Mohd. Rosli , Ngadi Norzita , Abdullah Mohd Ezree , Mohamed Abdullahi Ali
Published: March 2016

Aging process of bitumen is one of the main obstacles, which limit the implementation of porous pavement. An aging process would cause a shorter service life of porous asphalt compared to the conventional hot mix asphalt mixture. The tendency rate of aging processes in porous asphalt is high due to the exposure of bitumen and aggregates binding in an open-graded structure that maximizes oxidation process to occur thus producing aged binder. In this respect to restore the original characteristics of pavement from aged bitumen, rejuvenation of bitumen binder offers an effective option. From the previous research, the performance of waste cooking oil (WCO) is investigated and indicated as one of rejuvenator agents for bitumen regeneration. Thus, this paper reviewed the novelty of the WCO, as an alternative natural rejuvenating agent for aged bitumen to a condition that resembles the original bitumen in the asphalt mixture.
On-Chip Cytotoxicity Testing of Nepali Chiya Extract
Authors: Kim Sueon , Hyuk Jang In , Gu Lee Won
Published: March 2016

Here, we report a threshold limit value (TLV) of on-chip cytotoxicity of Nepali Chiya, the Nepali traditional black tea. To demonstrate our proof-of-concept validation, we used the active sealing chip with serial dilution that can directly perform on-chip cytotoxicity testing onto the cells cultured in a petri dish. In our experiments, the TLV for mortality on HeLa cells was observed as 400 μg/ml for Nepali Chiya extract. We believe this approach would be a rapid and simple method for on-chip TLV screening of potability of tea extract at the laboratory level, and furthermore as a new potential drug supplement in pharmaceutical industries.
Vibration Frequencies and Modes of a Z-Shaped Beam With Variable Folding Angles
Authors: Zhang W. , Hu W. H. , Cao D. X. , Yao M. H.
Published: March 2016

In this paper, we investigate the vibration characteristics of a Z-shaped beam with variable folding angles which is used to model a folding wing of a morphing aircraft under the condition of a fixed structure. The governing equations of motions for the Z-shaped beam are formulated. For a specific set of material and geometrical parameters, the first three in-plane and the first two out-of-plane linear frequencies of the Z-shaped beam are theoretically calculated, and validated by the experiments and numerical simulations. Additionally, the theoretical mode shapes at a fixed folding angle are compared to the experimental results and the finite element simulations. The theoretical results agree well with numerical simulations and experiments. The results obtained in this paper are helpful for designing and controlling Z-shaped beam structures, and can also be used as a basis to study the nonlinear dynamics of these structures.
Loss Mechanisms and Flow Control for Improved Efficiency of a Centrifugal Compressor at High Inlet Prewhirl
Authors: Zheng Xinqian , Huang Qiangqiang , Liu Anxiong
Published: March 2016

Variable inlet prewhirl is an effective way to suppress compressor flow instability. Compressors usually employ a high degree of positive inlet prewhirl to shift the surge line in the performance map to a lower mass flow region. However, the efficiency of a compressor at high inlet prewhirl is far lower than that at zero or low prewhirl. This paper investigates the performances of a centrifugal compressor with different prewhirls, discusses the mechanisms which are responsible for the production of extra loss induced by high inlet prewhirl and develops flow control methods to improve efficiency at high inlet prewhirl. The approach combines steady three-dimensional Reynolds average Navier–Stokes (RANS) simulations with theoretical analysis and modeling. In order to make the study universal to various applications with inlet prewhirl, the inlet prewhirl was imposed by modifying the velocity direction of inlet boundary condition. Simulation results show that the peak efficiency at high inlet prewhirl is reduced by over 7.6% points compared with that at zero prewhirl. The extra loss occurs upstream and downstream of the impeller. Severe flow separation, which reduces efficiency by 2.3% points, was found near the inlet hub. High inlet prewhirl works like a centrifuge gathering low-kinetic-energy fluid to hub, which induces the separation. A dimensionless parameter C was defined to measure the centrifugal trend of gas and indicate the flow separation near the inlet hub. As for the extra loss which is produced downstream of the impeller, the flow mismatch of impeller and diffuser at high prewhirl causes a violent backflow near the diffuser vanes' leading edges. An analytical model was built to predict diffuser choking mass flow. It proves that the diffuser has already operated unstably at high prewhirl. Based on these two loss mechanisms, the hub curve and the diffuser stager angle were modified and adjusted, respectively, for higher efficiency at high prewhirl. The efficiency improvement benefited from the modification of the hub is 1.1% points, and that benefited from the combined optimization is 2.4% points. During optimizing, constant distribution of inlet prewhirl was found to be another factor for inducing reverse flow at the leading edge of the impeller blade root, which turned out being blamed on the misalignment of the swirl angle and the blade angle.
Robust Exponential Stability of Large-Scale System With Mixed Input Delays and Impulsive Effect
Authors: Xue Huanbin , Zhang Jiye , Zheng Weifan , Hong Wang
Published: March 2016

In this paper, a class of large-scale systems with impulsive effect, input disturbance, and both variable and unbounded delays were investigated. On the assumption that all subsystems of the large-scale system can be exponentially stabilized, and the stabilizing feedbacks and corresponding Lyapunov functions (LFs) for the closed-loop systems are available, using the idea of vector Lyapunov method and M-matrix property, the intero-differential inequalities with variable and unbounded delays were constructed. By the stability analysis of the intero-differential inequalities, the sufficient conditions to ensure the robust exponential stability of the large-scale system were obtained. Finally, the correctness and validity of the methods was verified by two numerical examples.
A general model for stray dose calculation of static and intensity‐modulated photon radiation
Authors: Hauri Pascal , Hälg Roger A. , Besserer Jürgen , Schneider Uwe
Published: March 2016

Purpose:

There is an increasing number of cancer survivors who are at risk of developing late effects caused by ionizing radiation such as induction of second tumors. Hence, the determination of out‐of‐field dose for a particular treatment plan in the patient's anatomy is of great importance. The purpose of this study was to analytically model the stray dose according to its three major components.

Methods:

For patient scatter, a mechanistic model was developed. For collimator scatter and head leakage, an empirical approach was used. The models utilize a nominal beam energy of 6 MeV to describe two linear accelerator types of a single vendor. The parameters of the models were adjusted using ionization chamber measurements registering total absorbed dose in simple geometries. Whole‐body dose measurements using thermoluminescent dosimeters in an anthropomorphic phantom for static and intensity‐modulated treatment plans were compared to the 3D out‐of‐field dose distributions calculated by a combined model.

Results:

The absolute mean difference between the whole‐body predicted and the measured out‐of‐field dose of four different plans was 11% with a maximum difference below 44%. Computation time of 36 000 dose points for one field was around 30 s. By combining the model‐calculated stray dose with the treatment planning system dose, the whole‐body dose distribution can be viewed in the treatment planning system.

Conclusions:

The results suggest that the model is accurate, fast and can be used for a wide range of treatment modalities to calculate the whole‐body dose distribution for clinical analysis. For similar energy spectra, the mechanistic patient scatter model can be used independently of treatment machine or beam orientation.
Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition
Authors: Kahle Kristopher T. , Schmouth Jean-François , Lavastre Valérie , Latremoliere Alban , Zhang Jinwei , Andrews Nick , Omura Takao , Laganière Janet , Rochefort Daniel , Hince Pascale , Castonguay Geneviève , Gaudet Rébecca , Mapplebeck Josiane C. S. , Sotocinal Susana G. , Duan JingJing , Ward Catherine , Khanna Arjun R. , Mogil Jeffrey S. , Dion Patrick A. , Woolf Clifford J. , Inquimbert Perrine , Rouleau Guy A.
Published: March 2016

Mice lacking the HSN2 form of the kinase WNK1 are protected from neuropathic pain due to nerve injury.
New connections: Setting the GABA response
Authors: Gough Nancy R.
Published: March 2016

In the developing brain, WNK signaling enables GABA to enhance synaptic activity, but this same effect in the spinal cord contributes to neuropathic pain.
Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State
Authors: Yoon Gi S. , Keswani Rahul K. , Sud Sudha , Rzeczycki Phillip M. , Murashov Mikhail D. , Koehn Tony A. , Standiford Theodore J. , Stringer Kathleen A. , Rosania Gus R.
Published: March 2016

Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ therapy is accompanied by the formation of drug biocrystals that accumulate within resident tissue macrophages, without obvious toxicological manifestations. Therefore, to specifically elucidate the off-target consequences of drug bioaccumulation in macrophages, we compared the level of inflammasome activation in CFZ-accumulating organs (spleen, liver and lung) in mice after 2 and 8 weeks of CFZ treatment when the drug exists in soluble and insoluble (biocrystalline) forms, respectively. Surprisingly, the results showed a drastic reduction in caspase 1 and interleukin-1β (IL-1β) cleavage in the livers of mice treated with CFZ for 8 weeks (8-week-CFZ-treated mice) compared to 2-week-CFZ-treated and control mice, which was accompanied by a 3-fold increase in hepatic IL-1 receptor antagonist (IL-1RA) production and a 21-fold increase in serum IL-1RA levels. In the lung and spleen, IL-1β cleavage and tumor necrosis factor alpha expression were unaffected by soluble or biocrystal CFZ forms. Functionally, there was a drastic reduction of carrageenan- and lipopolysaccharide-induced inflammation in the footpads and lungs, respectively, of 8-week-CFZ-treated mice. This immunomodulatory activity of CFZ biocrystal accumulation was attributable to the upregulation of IL-1RA, since CFZ accumulation had minimal effect in IL-1RA knockout mice or 2-week-CFZ-treated mice. In conclusion, CFZ accumulation and biocrystal formation in resident tissue macrophages profoundly altered the host's immune system and prompted an IL-1RA-dependent, systemic anti-inflammatory response.
Efficacy of Artilysin Art-175 against Resistant and Persistent Acinetobacter baumannii
Authors: Defraine Valerie , Schuermans Joris , Grymonprez Barbara , Govers Sander K. , Aertsen Abram , Fauvart Maarten , Michiels Jan , Lavigne Rob , Briers Yves
Published: March 2016

Bacteriophage-encoded endolysins have shown promise as a novel class of antibacterials with a unique mode of action, i.e., peptidoglycan degradation. However, Gram-negative pathogens are generally not susceptible due to their protective outer membrane. Artilysins overcome this barrier. Artilysins are optimized, engineered fusions of selected endolysins with specific outer membrane-destabilizing peptides. Artilysin Art-175 comprises a modified variant of endolysin KZ144 with an N-terminal fusion to SMAP-29. Previously, we have shown the high susceptibility of
Pseudomonas aeruginosa
to Art-175. Here, we report that Art-175 is highly bactericidal against stationary-phase cells of multidrug-resistant
Acinetobacter baumannii
, even resulting in a complete elimination of large inocula (≥10
8
CFU/ml). Besides actively dividing cells, Art-175 also kills persisters. Instantaneous killing of
A. baumannii
upon contact with Art-175 could be visualized after immobilization of the bacteria in a microfluidic flow cell. Effective killing of a cell takes place through osmotic lysis after peptidoglycan degradation. The killing rate is enhanced by the addition of 0.5 mM EDTA. No development of resistance to Art-175 under selection pressure and no cross-resistance with existing resistance mechanisms could be observed. In conclusion, Art-175 represents a highly active Artilysin against both
A. baumannii
and
P. aeruginosa
, two of the most life-threatening pathogens of the order
Pseudomonadales
.
High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages
In Vitro
Authors: Farowski Fedja , Cornely Oliver A. , Hartmann Pia
Published: March 2016

Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function
in vitro
. In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of
Aspergillus fumigatus
conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of
Aspergillus
species infection warrants control of the pathogen and preservation of tissue integrity at the same time.
The tell-tale thigh
Authors: Scheurer Johannes , Stoevesandt Dietrich , Siekmann Holger , Kielstein Heike
Published: March 2016

A body of a 91-year-old donor underwent whole-body CT scanning before being transferred for use in an anatomical dissection course. Metallic objects were detected in the thigh muscles, extensive bone abnormalities were found in the left femur and the diaphysis of the left femur was 50% wider than that of the right diaphysis. History revealed that the body donor had been seriously wounded at the end of World War II by a rocket explosion. His multiple fractures and lesions had not been surgically treated either in an Austrian military hospital or in a French prisoner of war camp. The patient suffered for almost 70 years from this violation of the Geneva Conventions. In the light of current armed conflicts, the present case is an example of how one injustice can result in severe, lifelong medical consequences. It also shows that the history behind a wounded thigh can have an enormous impact on teaching ethics to today's medical students.
Combustible cigarettes cost less to use than e-cigarettes: global evidence and tax policy implications
Authors: Liber Alex C , Drope Jeffrey M , Stoklosa Michal
Published: March 2016

Background

Some scholars suggest that price differences between combustible cigarettes and e-cigarettes could be effective in moving current combustible smokers to e-cigarettes, which could reduce tobacco-related death and disease. Currently, in most jurisdictions, e-cigarettes are not subject to the same excise taxes as combustible cigarettes, potentially providing the category with a price advantage over combustible cigarettes. This paper tests whether e-cigarettes tax advantage has translated into a price advantage.

Methods

In a sample of 45 countries, the price of combustible cigarettes, disposable e-cigarettes and rechargeable cigarettes were compared.

Results

Comparable units of combustible cigarettes cost less than disposable e-cigarettes in almost every country in the sample. While the e-liquids consumed in rechargeable e-cigarettes might cost less per comparable unit than combustible cigarettes, the initial cost to purchase a rechargeable e-cigarette presents a significant cost barrier to switching from smoking to vaping.

Discussion

Existing prices of e-cigarettes are generally much higher than of combustible cigarettes. If policymakers wish to tax e-cigarettes less than combustibles, forceful policy action—almost certainly through excise taxation—must raise the price of combustible cigarettes beyond the price of using e-cigarettes.
Favorites and leftovers on the menu of scavenging seabirds: modelling spatiotemporal variation in discard consumption
Authors: Depestele Jochen , Rochet Marie-Joëlle , Dorémus Ghislain , Laffargue Pascal , Stienen Eric Willem Maria
Published: March 2016

Fishery discards subsidise the food supply of a large community of scavenging seabirds, thus substantially influencing seabird ecology. Seabird preference for certain types of discards determines the number and composition of discards available for non-avian marine scavengers. To quantify both portions of discards temporally as well as spatially, we have used a modelling framework that integrates the spatial and temporal variation in seabird distribution, seabird attraction to fishing vessels, and discard distribution. The framework was applied to a case study in the Bay of Biscay, where a wide variation in discard consumption was observed across seabird foraging guilds, discard types, periods, and locations. Seabirds removed about one-quarter of the Bay of Biscay discards. The remaining sinking discards have limited potential to subsidize scavenging benthic communities on a large scale, but they may contribute substantially to scavenger diets on a local scale. Changes in food subsidies caused by discard mitigation measures, such as the “landing obligation” in the European Common Fisheries Policy, are likely to have ecosystem effects on both scavenging seabirds and non-avian marine scavengers.
Pinocembrin attenuates gentamicin-induced nephrotoxicity in rats
Authors: Promsan Sasivimon , Jaikumkao Krit , Pongchaidecha Anchalee , Chattipakorn Nipon , Chatsudthipong Varanuj , Arjinajarn Phatchawan , Pompimon Wilart , Lungkaphin Anusorn
Published: March 2016

Oxidative stress mediated apoptosis of renal tubular cells is a major pathology of gentamicin-induced nephrotoxicity, which is one of the prevailing causes of acute renal failure. Pinocembrin is a major flavonoid found in rhizomes of fingerroot (Boesenbergia pandurata). It has pharmacological and biological activities including antimicrobial, anti-inflammatory, and antioxidant effects. Preclinical studies have suggested that pinocembrin protects rat brain and heart against oxidation and apoptosis induced by ischemia–reperfusion. The aim of the current study was to investigate the mechanisms of renoprotection elicited by pinocembrin in gentamicin-induced nephrotoxicity. Nephrotoxicity was induced in rats by intraperitoneal injection (i.p.) of gentamicin, and pinocembrin was administered via i.p. 30 min before gentamicin treatment for 10 days. Gentamicin-induced nephrotoxicity was indicated by the reduced renal function and renal Oat3 function and expression. Gentamicin treatment also stimulated Nrf2, HO-1, and NQO1, as well as the pro-apoptotic proteins Bax and caspase-3, concomitant with the attenuation of Bcl-XL expression in the renal cortical tissues. Pinocembrin pretreatment improved renal function and renal Oat3 function and reduced oxidative stress and apoptotic conditions. These findings indicate that pinocembrin has a protective effect against gentamicin-induced nephrotoxicity, which may be due in part to its antioxidant and anti-apoptotic effects, subsequently leading to improved renal function.
Ordinal Optimization with Computing Budget Allocation for Selecting an Optimal Subset
Authors: Almomani Mohammad H. , Alrefaei Mahmoud H.
Published: March 2016

In this paper, we consider the problem of selecting the top [Formula: see text] systems when the number of alternative systems is very large. We propose a sequential procedure that consists of two stages to solve this problem. The procedure is a combination of the ordinal optimization (OO) technique and optimal computing budget allocation (OCBA) method. In the first stage, the OO is used to select a subset that overlaps with the set of actual best [Formula: see text] systems with high probability. Then in the second stage the optimal computing budget is used to select the top [Formula: see text] systems from the selected subset. The proposed procedure is tested on two numerical examples. The numerical tests show that the proposed procedure is able to select a subset of best systems with high probability and short simulation time.
Online Work-Break Problem and its Competitive Analysis
Authors: Ma Weimin , Ji Xiaodong
Published: March 2016

An original online problem with decreasing profit growth rate is proposed to optimize the work hours of employees, named the online work-break problem (WBP). In this problem, the manager has to answer for an abstract worker when he should have a break for his work efficiency declines with the durative time of work period. The efficiency of the worker is presented by a work efficiency function [Formula: see text] in the description of our problem. We present the online algorithms to solve the WBP based on linear estimation of [Formula: see text] under two levels. Both the problems with single-period and dynamic multi-periods have 2-competitive online algorithms.
Quadratic temperature dependence of electronic heat capacities in the κ-type organic superconductors
Authors: Imajo Shusaku , Yamashita Satoshi , Akutsu Hiroki , Nakazawa Yasuhiro
Published: March 2016

We carried out a systematic measurement and data analysis of low-temperature heat capacities of three BEDT-TTF-based superconductive compounds with [Formula: see text]-type structure, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene so as to compare the character of the quasi-particle excitations reflected in the electronic heat capacity. We used an original relaxation calorimetry cell with much reduced addenda heat capacity as compared with previous works. The three compounds, [Formula: see text]-(BEDT-TTF)2Cu(NCS)2, [Formula: see text]-(BEDT-TTF)2Ag(CN)2H2O, [Formula: see text]-(BEDT-TTF)4Hg[Formula: see text]Br8 show distinct quadratic temperature dependence in their electronic heat capacity obtained by subtracting normal states data obtained by applying magnetic fields from the 0 T data. The line-nodal gap due to [Formula: see text]-wave pairing symmetry is suggested as common phenomena of the superconductivity of the [Formula: see text]-type compounds.
Efficient Constrained Combinatorial Auctions
Authors: Lerner Anat , Gonen Rica
Published: March 2016

The seminal work by Green and Laffont [(1977) characterization of satisfactory mechanisms for the revelation of preferences for public goods, Econometrica 45, 427–438] shows that efficient mechanisms with Vickrey–Clarke–Groves prices satisfy the properties of dominant-strategy incentive compatible (DSIC) and individually rational in the quasilinear utilities model. Nevertheless in many real-world situations some players have a gap between their willingness to pay and their ability to pay, i.e., a budget. We show that once budgets are integrated into the model then Green and Laffont’s theorem ceases to apply. More specifically, we show that even if only a single player has budget constraints then there is no deterministic efficient mechanism that satisfies the individual rationality and DSIC properties. Furthermore, in a quasilinear utilities model with [Formula: see text] nonidentical items and [Formula: see text] players with multidimensional types, we characterize the sufficient and necessary conditions under which Green and Laffont’s theorem holds in the presence of budget-constrained players. Interestingly our characterization is similar in spirit to that of Maskin [(2000) Auctions, development and privatization: Efficient auctions with liquidity-constrained buyers, Eur. Econ. Rev. 44, 667–681] for Bayesian single-item constrained-efficiency auctions.
On Application of Theory of Distributions to Static and Dynamic Analysis of Cracked Beams
Authors: Grossi Ricardo Oscar , Raffo Javier Leandro
Published: March 2016

This paper presents a rigorous study on the static and dynamic behavior of beams affected by cracks. The theory of distributions developed by Laurent Schwartz is adopted as it is particularly suitable for the treatment of discontinuities in functions for the deflection and derivatives of the beam. Thus, this paper presents a contribution towards the understanding and application of the theory of distributions to the static and dynamic behavior of structural elements affected by cracks. A simple, computationally efficient and accurate algorithm is developed for the problems of concern. Numerical results are presented for beams with two cracks. The algorithms developed for beams with discontinuities are obtained in a rigorous framework for static and vibration problems.
Damage Index Evaluation of Concrete Gravity Dam Based on Hysteresis Behavior and Stiffness Degradation Under Cyclic Loading
Authors: Ansari MD. Imteyaz , Agarwal Pankaj
Published: March 2016

An assessment of seismic vulnerability of concrete gravity dams based on the fragility curves needs a well-defined damage index (DI) to define different states of damage. The DI formulation for other types of structures is not applicable to concrete gravity dams due to the change in failure mechanism. In this study, a definition of DI based on the factor of safety against sliding is attempted and correlated with the DI formulation based on the natural period of the structure and the maximum crest displacement with cumulative energy dissipation. The proposed DI relies on the nonlinear behavior of the concrete gravity dam model under cyclic testing. The hysteresis behavior is also verified through the finite element analysis by considering the damaged plasticity behavior of concrete.
Reciprocal complementary distance equienergetic graphs
Authors: Ramane Harishchandra S. , Gudodagi Gouramma A.
Published: March 2016

The reciprocal complementary distance (RCD) matrix of a graph [Formula: see text] is defined as [Formula: see text], in which [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text], where [Formula: see text] is the diameter of [Formula: see text] and [Formula: see text] is the distance between the [Formula: see text]th and [Formula: see text]th vertex of [Formula: see text]. The [Formula: see text]-energy [[Formula: see text]] of [Formula: see text] is defined as the sum of the absolute values of the eigenvalues of RCD-matrix of [Formula: see text]. Two graphs [Formula: see text] and [Formula: see text] are said to be RCD-equienergetic if [Formula: see text]. In this paper, we obtain the RCD-eigenvalues and RCD-energy of the join of certain regular graphs and thus construct the non-RCD-cospectral, RCD-equienergetic graphs on [Formula: see text] vertices, for all [Formula: see text].
Schrödinger–Poisson system with potential of critical growth
Authors: Hassani Abdessamad , Iskafi Khalid
Published: March 2016

In this paper, we consider a Schrödinger–Poisson system with nonlinear potential of critical growth, and we prove existence of positive solution with positive energy by using the Ekeland variational principle and the Mountain-Pass theorem.
The theory of direct magnetoelectric effect in the bilayer system of ferromagnetic–piezoelectric
Authors: Nechaev V. N. , Shuba A. V.
Published: March 2016

The theory of direct magnetoelectric (ME) effect in a bilayer of ferromagnetic and piezoelectric is developed taking into account nonuniform distribution of electrical field on a piezoelectric layer thickness. The simultaneous solution of the motion equations for piezoelectric and ferromagnetic mediums allowed to numerically and analytically calculate the dependence of natural mechanical oscillation on structure parameters and to determine the dependence of ME effect coefficient on frequency of the variable magnetic field.
Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction
Authors: Bergeron John J.M. , Di Guglielmo Gianni M. , Dahan Sophie , Dominguez Michel , Posner Barry I.
Published: March 2016

Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs) exemplify how receptor location is coupled to signal transduction. Extracellular binding of ligands to these RTKs triggers their concentration into vesicles that bud off from the cell surface to generate intracellular signaling endosomes. On the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects the downstream signaling proteins and lipids to effect growth factor and polypeptide hormone action. This selection is followed by the recruitment of protein tyrosine phosphatases that inactivate the RTKs and deliver them by membrane fusion and fission to late endosomes. Coincidentally, proteinases inside the endosome cleave the EGF and insulin ligands. Subsequent inward budding of the endosomal membrane generates multivesicular endosomes. Fusion with lysosomes then results in RTK degradation and downregulation. Through the spatial positioning of RTKs in target cells for EGF and insulin action, the temporal extent of signaling, attenuation, and downregulation is regulated.
Ten Years of Grid Cells
Authors: Rowland David C. , Roudi Yasser , Moser May-Britt , Moser Edvard I.
Published: March 2016

The medial entorhinal cortex (MEC) creates a neural representation of space through a set of functionally dedicated cell types: grid cells, border cells, head direction cells, and speed cells. Grid cells, the most abundant functional cell type in the MEC, have hexagonally arranged firing fields that tile the surface of the environment. These cells were discovered only in 2005, but after 10 years of investigation, we are beginning to understand how they are organized in the MEC network, how their periodic firing fields might be generated, how they are shaped by properties of the environment, and how they interact with the rest of the MEC network. The aim of this review is to summarize what we know about grid cells and point out where our knowledge is still incomplete.
Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?
Authors: Zlebnik Natalie E. , Cheer Joseph F.
Published: March 2016

The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia. Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders. Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD). Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders. Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression. Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.
The Diplomacy of War and Peace
Authors: Trager Robert F.
Published: March 2016

Two broad traditions of scholarship can be distinguished in the vast literature on the diplomacy of conflict. The diplomatic communication tradition takes the difficulty of credible communication between adversaries as its central problem and analyzes the conditions for informative costly, costless, and inadvertent signals as well as the effects on conflict processes of these different forms of communication. A body of empirical work, focused particularly on public coercive diplomacy and alliances, also belongs to this approach. The other tradition is the rhetorical-argumentative, which focuses on rhetorical style, justificatory argument, and the effects of modes of discourse. These traditions have offered very different insights and, in some areas, complement and reinforce each other.
Does Big Data Change the Privacy Landscape? A Review of the Issues
Authors: Keller Sallie Ann , Shipp Stephanie , Schroeder Aaron
Published: March 2016

The current data revolution is changing the conduct of social science research as increasing amounts of digital and administrative data become accessible for use. This new data landscape has created significant tension around data privacy and confidentiality. The risk–utility theory and models underpinning statistical disclosure limitation may be too restrictive for providing data confidentially owing to the growing volumes and varieties of data and the evolving privacy policies. Science and society need to move to a trust-based approach from which both researchers and participants benefit. This review discusses the explosive growth of the new data sources and the parallel evolution of privacy policy and governance, with a focus on access to data for research. We provide a history of privacy policy, statistical disclosure limitation research, and record linkage in the context of this brave new world of data.
T Cell Repertoire and Inflammatory Bowel Disease
Authors: Croitoru Kenneth , Wong David KH , Baca-Estrada Maria E
Published: March 2016

The diversity of the T cell receptor repertoire is generated through rearrangement of the variable, junctional and constant region genes. Selection processes in the thymus and periphery serve to eliminate self‐reacting T cells, thereby preventing autoimmune disease. The possibility that inflammatory bowel disease (IBD) is an autoimmune disease has led to the search for an auto‐antigen. In addition, studies are exploring the T cell receptor repertoire in IBD patients for changes that may provide clues regarding etiopathogenesis. Using monoclonal antibodies to T cell receptor variable‐gene products or polymerase chain reaction analysis of variable‐gene mRNA expression, the mucosal T cell repertoire has been examined in humans. The intestinal intraepithelial lymphocytes show a significant degree of oligoclonal expansion that may represent local antigen exposure or unique selection processes. This is in keeping with studies that show that murine intestinal intraepithelial lymphocytes undergo positive and possibly negative selection independent of the thymus. In the inflamed human gut, shifts in the T cell receptor repertoire may also reflect recruitment of peripheral T cells to the gut. In one study, a subset of Crohn’s disease patients was shown to have an increase in the proportion of variable β8 peripheral blood lymphocyte and mesenteric lymph node cells, suggesting a superantigen effect. The authors hypothesized that changes in the functional T cell receptor repertoire can also occur which might be independent of changes in the distribution of T cells expressing variable β T cell receptors. In fact, the authors have shown there is a selective decrease in the cytotoxic function of peripheral variable β8 T cells in Crohn’s disease. Furthermore, stimulation with the variable β8 selective bacterial enterotoxin staphylococcal enterotoxin E failed to increase the cytotoxic function in this subset of Crohn’s disease patients compared with controls. This suggests that in Crohn’s disease, variable β8 T cells have undergone an alteration in function that may reflect previous exposure to a superantigen‐like stimulus. The relationship to the etiology and pathogenesis of IBD remains to be defined.
IgG4 Related Lung Disease
Authors: Patel Mihir , Kumar Beena , Diep My Linh , Nandurkar Deepali
Published: March 2016

IgG4 related disease is a poorly understood immune mediated condition. Lung involvement is rare and difficult to diagnose and can mimic primary lung malignancy on imaging. A patient who was found to have an incidental lung lesion with risk factors for primary pulmonary malignancy is reported.