bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges to develop novel anti‐inflammatory and analgesic drugs
Authors: Botz Bálint , Bölcskei Kata , Helyes Zsuzsanna 
Published: August 2016

Chronic inflammatory diseases and persistent pain of different origin represent common medical, social, and economic burden, and their pharmacotherapy is still an unresolved issue. Therefore, there is a great and urgent need to develop anti‐inflammatory and analgesic agents with novel mechanisms of action, but it is a very challenging task. The main problem is the relatively large translational gap between the preclinical experimental data and the clinical results due to characteristics of the models, difficulties with the investigational techniques particularly for pain, as well as species differences in the mechanisms. We summarize here the current state‐of‐the‐art medication and related ongoing strategies, and the novel targets with lead molecules under clinical development. The first members of the gold‐standard categories, such as nonsteroidal anti‐inflammatory drugs, glucocorticoids, and opioids, were introduced decades ago, and since then very few drugs with novel mechanisms of action have been successfully taken to the clinics despite considerable development efforts. Several biologics targeting different key molecules have provided breakthrough in some autoimmune/inflammatory diseases, but they are expensive, only parenterally available, their long‐term side effects often limit their administration, and they do not effectively reduce pain. Some kinase inhibitors and phosphodiesterase‐4 blockers have recently been introduced as new directions. There are in fact some promising novel approaches at different clinical stages of drug development focusing on transient receptor potential vanilloid 1/ankyrin 1 channel antagonism, inhibition of voltage‐gated sodium/calcium channels, several enzymes (kinases, semicarbazide‐sensitive amine oxidases, and matrix metalloproteinases), cytokines/chemokines, transcription factors, nerve growth factor, and modulation of several G protein‐coupled receptors (cannabinoids, purinoceptors, and neuropeptides). WIREs Nanomed Nanobiotechnol 2017, 9:e1427. doi: 10.1002/wnan.1427This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease
Carboxyl-terminal domain characterization of polyene-specific P450 hydroxylase in Pseudonocardia autotrophica
Authors: Kim Min-Kyung , Won Hyung-Jin , Kim Hye-Jin , Choi Si-Sun , Lee Heung-Shick , Kim Pil , Kim Eung-Soo 
Published: August 2016

Abstract
A polyene compound NPP identified in Pseudonocardia autotrophica was shown to contain an aglycone identical to nystatin, but to harbor a unique disaccharide moiety that led to higher solubility and reduced hemolytic activity. Recently, it was revealed that the final step of NPP (nystatin-like polyene) biosynthesis is C10 regio-specific hydroxylation by the cytochrome P450 hydroxylase (CYP) NppL (Kim et al. [7]). Through mutation and cross-complementation, here we found that NppL preferred a polyene substrate containing a disaccharide moiety for C10 hydroxylation, while its orthologue NysL involved in nystatin biosynthesis showed no substrate preference toward mono- and disaccharide moieties, suggesting that two homologous polyene CYPs, NppL and NysL might possess a unique domain recognizing a sugar moiety. Two hybrid NppL constructs containing the C-terminal domain of NysL exhibited no substrate preference toward 10-deoxy NPP and 10-deoxy nystatin-like NysL, implying that the C-terminal domain plays a major role in differentiating the sugar moiety responsible for substrate specificity. Further C-terminal domain dissection of NppL revealed that the last fifty amino acids play a critical role in determining substrate specificity of polyene-specific hydroxylation, setting the stage for the biotechnological application of hydroxyl diversification for novel polyene biosynthesis in actinomycetes.
Protective effects of oridonin on the sepsis in mice
Authors: Zhao Yan‐Jun , Lv Hu , Xu Ping‐Bo , Zhu Min‐Min , Liu Yi , Miao Chang‐Hong , Zhu Yun 
Published: August 2016

AbstractThis study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)‐induced sepsis in mice. Male C57BL/6 mice weighing 22–30 g and aged 8–10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin–eosin staining of the lung, detection of lung wet‐to‐dry ratio, and serum cytokines (tumor necrosis factor [TNF]‐α and interleukin [IL]‐6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet‐to‐dry ratio, decreased serum TNF‐α and IL‐6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7‐day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.
Religion in the boardroom and its impact on Islamic banks' performance
Authors: Ali Mohsin , Azmi Wajahat 
Published: August 2016

AbstractThe impact of board diversity, in terms of gender, race, ethnicity etc., on performance and stability of firms has been researched extensively. However, the impact of religious diversity and its impact on performance and stability has been completely ignored. This issue is quite relevant, especially for the Islamic banks because of their primary objective i.e. to be in compliant with Islamic principles in all their dealings. Taking a cue from this argument, we believe if the majority board members are Muslim it can have a positive impact on the performance as they would better understand the importance of the substance of the shari'ah compliant dealings and that can translate into good performance and make it more stable. Based on our arguments, we examined the impact of religious diversity on the performance and stability on Malaysian banks Islamic and Conventional both for the period of 9 years, through 2005 to 2013. Our results from GMM estimation reveal that the religious orientation has no impact on the performance and this result is robust to various proxies. Our results imply that a non‐Muslim member of the board of directors is able to run the Islamic banking business as good as a Muslim board member.
A FORM OF MULTIVARIATE PARETO DISTRIBUTION WITH APPLICATIONS TO FINANCIAL RISK MEASUREMENT
Authors: Su Jianxi , Furman Edward 
Published: August 2016

AbstractA new multivariate distribution possessing arbitrarily parametrized and positively dependent univariate Pareto margins is introduced. Unlike the probability law of Asimitet al. (2010), the structure in this paper is absolutely continuous with respect to the corresponding Lebesgue measure. The distribution is of importance to actuaries through its connections to the popular frailty models, as well as because of the capacity to describe dependent heavy-tailed risks. The genesis of the new distribution is linked to a number of existing probability models, and useful characteristic results are proved. Expressions for, e.g., the decumulative distribution and probability density functions, (joint) moments and regressions are developed. The distributions of minima and maxima, as well as, some weighted risk measures are employed to exemplify possible applications of the distribution in insurance.
Small-scale anisotropy in turbulent boundary layers
Authors: Pumir Alain , Xu Haitao , Siggia Eric D. 
Published: August 2016

In a channel flow, the velocity fluctuations are inhomogeneous and anisotropic. Yet, the small-scale properties of the flow are expected to behave in an isotropic manner in the very-large-Reynolds-number limit. We consider the statistical properties of small-scale velocity fluctuations in a turbulent channel flow at moderately high Reynolds number ($Re_{\unicode[STIX]{x1D70F}}\approx 1000$), using the Johns Hopkins University Turbulence Database. Away from the wall, in the logarithmic layer, the skewness of the normal derivative of the streamwise velocity fluctuation is approximately constant, of order 1, while the Reynolds number based on the Taylor scale is$R_{\unicode[STIX]{x1D706}}\approx 150$. This defines a small-scale anisotropy that is stronger than in turbulent homogeneous shear flows at comparable values of$R_{\unicode[STIX]{x1D706}}$. In contrast, the vorticity–strain correlations that characterize homogeneous isotropic turbulence are nearly unchanged in channel flow even though they do vary with distance from the wall with an exponent that can be inferred from the local dissipation. Our results demonstrate that the statistical properties of the fluctuating velocity gradient in turbulent channel flow are characterized, on one hand, by observables that are insensitive to the anisotropy, and behave as in homogeneous isotropic flows, and on the other hand by quantities that are much more sensitive to the anisotropy. How this seemingly contradictory situation emerges from the simultaneous action of the flux of energy to small scales and the transport of momentum away from the wall remains to be elucidated.
The impact of the top management teams’ knowledge and experience on strategic decisions and performance
Authors: Li Peng-Yu 
Published: August 2016

AbstractThis paper explores whether top management teams’ (TMTs) knowledge and experience are significant predictors of a firm’s strategic decisions and organization outcomes. The existing research throws little light on how firms with limited resources embedded in TMTs, particularly in emerging markets, innovate and achieve success in foreign countries. We focus on the impact of TMTs’ functional background heterogeneity and international experience on innovation and internationalization, as well as examine the relationship between innovation, internationalization and performance. The proposed relationships are empirically investigated in a sample of Taiwanese-listed companies operating in the electronics industry. The results demonstrate a positive association between a TMT’s functional background heterogeneity and a firm’s innovation. Moreover, a TMT’s international experience relates positively to a firm’s innovation and internationalization, therefore firms with a higher level of innovation achieve a higher level of internationalization.
Triggers of Smoking Lapses Over the Course of a Quit Attempt
Authors: Ferguson Stuart G. , Shiffman Saul , Blizzard Leigh 
Published: August 2016

Introduction: Both withdrawal severity and smoking cues can trigger lapses. However, the temporal relationship between these two sets of triggers is unknown.Aims: To explore the time course of lapse triggers during a quit attempt.Methods: Across two cessation studies, 186 lapsers monitored their smoking in real-time for up to 7 weeks over the course of a quit attempt. During lapses, participants were asked to report the primary trigger of the event; this, including the time of the event relative to quit day, was logged by an electronic diary. Log multinomial regression was used to estimate the probability that each lapse would be withdrawal-triggered or cue-triggered.Results: Log multinomial regression showed that the probability of a first lapse being triggered by withdrawal rose in the initial days of a quit attempt before dropping as the quit attempt progressed (P < 0.01). The probability of a cue-triggered lapse rose over the course of a quit attempt (P < 0.05).Conclusions: The results are consistent both with the time course of withdrawal symptoms and with theoretical predictions about the relationship between nicotine dependence and stimulus control. The results have implications for tailoring smoking-cessation treatments; in particular, for the stepwise provision of smoking-cessation assistance over the course of a quit attempt.
Political Attitudes and Behaviour in a Non-Partisan Environment: Toronto 2014
Authors: McGregor R. Michael , Moore Aaron A. , Stephenson Laura B. 
Published: August 2016

AbstractVoting behaviour in municipal elections is understudied in Canada. Existing research is limited by the type of data (aggregate instead of individual-level) and the cases evaluated (partisan when most contests are non-partisan). The objective of this study is to contribute to this literature by using individual-level data about a non-partisan election. To do so, we use data from the Toronto Election Study, conducted during the 2014 election. Our research goals are to evaluate whether a standard approach to understanding vote choice (the multi-stage explanatory model) is applicable in a non-partisan, municipal-level contest, and to determine the correlates of vote choice in the 2014 Toronto mayoral election in particular. Our analysis reveals that, although it was a formally non-partisan contest, voters tended to view the mayoral candidates in both ideological and partisan terms. We also find that a standard vote choice model provides valuable insight into voter preferences at the municipal level.
Effect of transverse magnetic fields on high-harmonic generation in intense laser–solid interaction
Authors: Mu J. , Li F.-Y. , Sheng Z.-M. , Zhang J. 
Published: August 2016

AbstractThe effect of transverse magnetic fields on surface high-harmonic generation in intense laser–solid interactions is investigated. It is shown that the longitudinal motion of electrons can be coupled with the transverse motion via the magnetic fields, which lead to even-order harmonics under normal laser incidence. The dependence of the coupling efficiency and hence even harmonic generation with preplasma scale length and magnetic field strength are presented based upon particle-in-cell simulations. When the magnetic field is parallel to the laser electric field, the spectral intensity of the second harmonic is proportional to the magnetic field strength in a wide range up to 160 MG, while the situation with the magnetic field perpendicular to the laser electric field is more complicated. The second harmonic generation due to the magnetic field also tends to increase with the plasma density scale lengths, which is different from the high-harmonic generation by the oscillating mirror mechanism. With the increase of the laser spot size from a laser wavelength λL, both the magnetic field-induced harmonics and oscillating mirror high harmonics tend to increase first and then become saturated after 3λL. The magnetic field-induced second harmonic may be used to evaluate large self-generated magnetic fields developed near the critical density region and the preplasma conditions.
Vlasov–Maxwell simulations of backward Raman amplification of seed pulses in plasmas
Authors: Shoucri Magdi , Afeyan Bedros 
Published: August 2016

AbstractWe study the problem of the amplification of an ultra-short seed pulse via stimulated Raman backscattering (SRB) from a long pump pulse (assumed to have an envelope with a constant amplitude), in an underdense plasma. The SRB interaction couples the pump light wave to a daughter light seed wave propagating in the opposite direction, scattered off an electron plasma wave. In recent numerical simulations, it has been observed that besides stimulated Raman backward scattering (SRBS) and stimulated Raman forward scattering, other high-frequency kinetic instabilities can occur when modified distribution functions exist during the evolution of the system. In particular, we showed the prominent role played by kinetic electrostatic electron nonlinear (KEEN) waves (Afeyan et al., 2004). We continue this work by applying a relativistic Vlasov–Maxwell code to study stimulated KEEN wave scattering (SKEENS) and its role in the SRBS short pulse amplification processes. An analysis of the full spectrum of waves participating in the amplification processes is presented. The absence of spurious noise in grid-based Vlasov codes allows us to follow the evolution of the system with a kinetic (collisionless) description. This affords us a glimpse at the intricate phase-space structures such as trapped particle orbits, which coexist and interact nonlinearly in the electron distribution function.
“Let's Change the Law”: Arkansas and the Puzzle of Juvenile Justice Reform in the 1990s
Authors: Tanenhaus David S. , Nystrom Eric C. 
Published: August 2016

[Governor Tucker] should also propose that juveniles be charged as adults more often. Such laws sound harsh. They are. Right now, they need to be. This is known as protecting the public safety. As deterrence. Until that improbable day when social scientists pinpoint the cause of crime, punishment is the best answer. Sure, swift punishment. Word will get around.Arkansas Democrat-Gazette, August 10, 1994.
Which Wilson Do We (Dis)Honor?
Authors: Eisenach Eldon J. 
Published: August 2016

Woodrow Wilson is the only American political scientist to have served as President of the United States. In the time between his political science Ph.D. (from Johns Hopkins, in 1886) and his tenure as president (1913–21), he also served as president of Princeton University (1902–10) and president of the American Political Science Association (1909–10). Wilson is one of the most revered figures in American political thought and in American political science. The Woodrow Wilson Award is perhaps APSA’s most distinguished award, given annually for the best book on government, politics, or international affairs published in the previous year, and sponsored by the Woodrow Wilson Foundation at Princeton University.Wilson has also recently become the subject of controversy, on the campus of Princeton University, and in the political culture more generally, in connection with racist statements that he made and the segregationist practices of his administration. A group of Princeton students associated with the “Black Lives Matter” movement has demanded that Wilson’s name be removed from two campus buildings, one of which is the famous Woodrow Wilson School of Public and International Affairs (see Martha A. Sandweiss, “Woodrow Wilson, Princeton, and the Complex Landscape of Race,” http://www.thenation.com/article/woodrow-wilson-princeton-and-the-complex-landscape-of-race/). Many others have resisted this idea, noting that Wilson is indeed an important figure in the history of twentieth-century liberalism and Progressivism in the United States.A number of colleagues have contacted me suggesting that Perspectives ought to organize a symposium on the Wilson controversy. Although we do not regularly organize symposia around current events, given the valence of the controversy and its connection to issues we have featured in our journal (see especially the September 2015 issue on “The American Politics of Policing and Incarceration”), and given Wilson's importance in the history of our discipline, we have decided to make an exception in this case. We have thus invited a wide range of colleagues whose views on this issue will interest our readers to comment on this controversy. —Jeffrey C. Isaac, Editor.
How We Remember (and Forget) in Our Public History
Authors: Nunnally Shayla C. 
Published: August 2016

Woodrow Wilson is the only American political scientist to have served as President of the United States. In the time between his political science Ph.D. (from Johns Hopkins, in 1886) and his tenure as president (1913–21), he also served as president of Princeton University (1902–10) and president of the American Political Science Association (1909–10). Wilson is one of the most revered figures in American political thought and in American political science. The Woodrow Wilson Award is perhaps APSA’s most distinguished award, given annually for the best book on government, politics, or international affairs published in the previous year, and sponsored by the Woodrow Wilson Foundation at Princeton University.Wilson has also recently become the subject of controversy, on the campus of Princeton University, and in the political culture more generally, in connection with racist statements that he made and the segregationist practices of his administration. A group of Princeton students associated with the “Black Lives Matter” movement has demanded that Wilson’s name be removed from two campus buildings, one of which is the famous Woodrow Wilson School of Public and International Affairs (see Martha A. Sandweiss, “Woodrow Wilson, Princeton, and the Complex Landscape of Race,” http://www.thenation.com/article/woodrow-wilson-princeton-and-the-complex-landscape-of-race/). Many others have resisted this idea, noting that Wilson is indeed an important figure in the history of twentieth-century liberalism and Progressivism in the United States.A number of colleagues have contacted me suggesting that Perspectives ought to organize a symposium on the Wilson controversy. Although we do not regularly organize symposia around current events, given the valence of the controversy and its connection to issues we have featured in our journal (see especially the September 2015 issue on “The American Politics of Policing and Incarceration”), and given Wilson's importance in the history of our discipline, we have decided to make an exception in this case. We have thus invited a wide range of colleagues whose views on this issue will interest our readers to comment on this controversy. —Jeffrey C. Isaac, Editor.
The use of secondary metabolites extracted from Trichoderma for plant growth promotion in the Andean highlands
Authors: Ortuño Noel , Castillo José Antonio , Miranda Claudia , Claros Mayra , Soto Ximena 
Published: August 2016

AbstractAgriculture in the Altiplano and Andean Mountains is experiencing threats to sustainability mainly due to intensive cultivation of quinoa driven by international markets. This recent export-oriented production system is causing the degradation of soils and reducing productivity, therefore, agro-technological innovations are necessary to sustain cropping systems while maintaining organic quality (mostly quinoa). In this work, we searched for native Trichoderma species associated with plants from the Andean highlands to obtain an environmentally friendly and organic alternative to chemical fertilizers. We obtained different Trichoderma isolates from quinoa, potato and maize roots and soil, which were identified as Trichoderma harzianum, as well as other species. Twelve of the isolates were cultured in pairs to stimulate the production and secretion of compounds of diverse chemical nature that we called collectively ‘secondary metabolites’ (SMs). Crude extracts of SMs were used to inoculate selected crops to determine their plant growth promoting potential compared with two commercially available controls, chemical fertilizer and a bio-fertilizer. Results showed that SMs significantly promoted lettuce and radish growth and increased quinoa grain yield. Indole acetic acid was detected in all SM extracts that promoted plant growth, suggesting that this plant regulator might be responsible for the plant growth promoting activity. In conclusion, the Trichoderma-derived SMs approach appears to be a promising, simple and accessible technology for small-scale farmers in order to insure the sustainability, affordability and accessibility of food production in the Andes.