bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Src-kinase inhibition in cancer-induced bone pain
Authors: De Felice Milena , Lambert Daniel , Holen Ingunn , Escott K Jane , Andrew David 
Published: April 2016

Background Bone metastases occur frequently in advanced breast, lung, and prostate cancer, with approximately 70% of patients affected. Pain is a major symptom of bone metastases, and current treatments may be inadequate or have unacceptable side effects. The mechanisms that drive cancer-induced bone pain are not fully understood; however, it is known that there is sensitization of both peripheral bone afferents and central spinal circuits. It is well established that the N-methyl-D-aspartate receptor plays a major role in the pathophysiology of pain hypersensitivity. Inhibition of the non-receptor tyrosine kinase Src controls N-methyl-D-aspartate receptor activity and inhibiting Src reduces the hypersensitivity associated with neuropathic and inflammatory pains. As Src is also implicated in osteoclastic bone resorption, we have investigated if inhibiting Src ameliorates cancer-induced bone pain. We have tested this hypothesis using an orally bioavailable Src inhibitor (saracatinib) in a rat model of cancer-induced bone pain. Results Intra-tibial injection of rat mammary cancer cells (Mammary rat metastasis tumor cells -1), but not vehicle, in rats produced hindpaw hypersensitivity to thermal and mechanical stimuli that was maximal after six days and persisted for at least 13 days postinjection. Daily oral gavage with saracatinib (20 mg/kg) beginning seven days after intra-tibial injection reversed the thermal hyperalgesia but not the mechanical allodynia. The analgesic mechanisms of saracatinib appear to be due to an effect on the nervous system as immunoblotting of L2-5 spinal segments showed that mammary rat metastasis tumor cells-1 injection induced phosphorylation of the GluN1 subunit of the N-methyl-D-aspartate receptor, indicative of receptor activation, and this was reduced by saracatinib. Additionally, histology showed no anti-tumor effect of saracatinib at any dose and no significant effect on bone preservation. Conclusions This is the first demonstration that Src plays a role in the development of cancer-induced bone pain and that Src inhibition represents a possible new analgesic strategy for patients with bone metastases.
Rho/ROCK acts downstream of lysophosphatidic acid receptor 1 in modulating P2X3 receptor-mediated bone cancer pain in rats
Authors: Wu Jing-xiang , Yuan Xiao-min , Wang Qiong , Wei Wang , Xu Mei-ying 
Published: April 2016

Background Lysophosphatidic acid receptor 1 and Rho/ROCK signaling is implicated in bone cancer pain development. However, it remains unknown whether the two signaling pathways function together in P2X3 receptor-mediated bone cancer pain. Results In this study, using a rat model of bone cancer, we examined the expression of P2X3 and lysophosphatidic acid receptor 1 in rat dorsal root ganglion neurons and further dissected whether lysophosphatidic acid receptor 1 and Rho/ROCK-mediated pathways interacted in modulating rat pain behavior. Bone cancer was established by inoculating Walker 256 cells into the left tibia of female Wistar rats. We observed a gradual and yet significant decline in mean paw withdrawal threshold in rats with bone cancer, but not in control rats. Our immunohistochemical staining revealed that the number of P2X3- and lysophosphatidic acid receptor 1-positive dorsal root ganglion neurons was significantly greater in rats with bone cancer than control rats. Lysophosphatidic acid receptor 1 blockade with VPC32183 significantly attenuated decline in mean paw withdrawal threshold. Flinching behavior test further showed that lysophosphatidic acid receptor 1 inhibition with VPC32183 transiently but significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Rho inhibition by intrathecal BoTXC3 caused a rapid reversal in decline in mean paw withdrawal threshold of rats with bone cancer. Flinching behavior test showed that BoTXC3 transiently and significantly attenuated α,β-meATP-induced increase in paw lift time per minute. Similar findings were observed with ROCK inhibition by intrathecal Y27632. Furthermore, VPC32183 and BoTXC3 effectively aborted the appearance of lysophosphatidic acid-induced calcium influx peak. Conclusions Lysophosphatidic acid and its receptor LPAR1, acting through the Rho-ROCK pathway, regulate P2X3 receptor in the development of both mechanical and spontaneous pain in bone cancer.
Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve
Authors: Gresle Melissa M , Liu Yaou , Kilpatrick Trevor J , Kemper Dennis , Wu Qi-Zhu , Hu Bing , Fu Qing-Ling , So Kwok-Fai , Sheng Guoqing , Huang Guanrong , Pepinsky Blake , Butzkueven Helmut , Mi Sha 
Published: April 2016

Background Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. Objective In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. Methods The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. Results In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. Conclusion These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.
The Current Landscape of US Pediatric Anesthesiologists: Demographic Characteristics and Geographic Distribution
Authors: Muffly Matthew K. , Muffly Tyler M. , Weterings Robbie , Singleton Mark , Honkanen Anita 
Published: April 2016

BACKGROUND:
There is no comprehensive database of pediatric anesthesiologists, their demographic characteristics, or geographic location in the United States.

METHODS:
We endeavored to create a comprehensive database of pediatric anesthesiologists by merging individuals identified as US pediatric anesthesiologists by the American Board of Anesthesiology, National Provider Identifier registry, Healthgrades.com database, and the Society for Pediatric Anesthesia membership list as of November 5, 2015. Professorial rank was accessed via the Association of American Medical Colleges and other online sources. Descriptive statistics characterized pediatric anesthesiologists’ demographics. Pediatric anesthesiologists’ locations at the city and state level were geocoded and mapped with the use of ArcGIS Desktop 10.1 mapping software (Redlands, CA).

RESULTS:
We identified 4048 pediatric anesthesiologists in the United States, which is approximately 8.8% of the physician anesthesiology workforce (n = 46,000). The median age of pediatric anesthesiologists was 49 years (interquartile range, 40–57 years), and the majority (56.4%) were men. Approximately two-thirds of identified pediatric anesthesiologists were subspecialty board certified in pediatric anesthesiology, and 33% of pediatric anesthesiologists had an identified academic affiliation. There is substantial heterogeneity in the geographic distribution of pediatric anesthesiologists by state and US Census Division with urban clustering.

CONCLUSIONS:
This description of pediatric anesthesiologists’ demographic characteristics and geographic distribution fills an important gap in our understanding of pediatric anesthesia systems of care.
The Potential of Servicizing as a Green Business Model
Authors: Agrawal Vishal V. , Bellos Ioannis 
Published: April 2016

It has been argued that servicizing business models, under which a firm sells the use of a product rather than the product itself, are environmentally beneficial. The main arguments are as follow. First, under servicizing the firm charges customers based on the product usage. Second, the quantity of products required to meet customer needs may be smaller because the firm may be able to pool customer needs. Third, the firm may have an incentive to offer products with higher efficiency. Motivated by these arguments, we investigate the economic and environmental potential of servicizing business models. We endogenize the firm’s choice between a pure sales model, a pure servicizing model, and a hybrid model with both sales and servicizing options; the pricing decisions; and the resulting customer usage. We consider two extremes of pooling efficacy, i.e., no pooling versus strong pooling. We find that under no pooling servicizing leads to higher environmental impact due to production but lower environmental impact due to use. In contrast, under strong pooling, when a hybrid business model is more profitable, it is also environmentally superior. However, a pure servicizing model is environmentally inferior for high production costs because it leads to a larger production quantity even under strong pooling. We also examine the product efficiency choice and find that the firm offers higher efficiency products only under servicizing models with strong pooling. This paper was accepted by Serguei Netessine, operations management.
Jerarquía católica y oligarquía municipal ante el control de la Universidad de Valencia (el obispo Esteve y la cuestión de los pasquines contra el patriarca Ribera)
Authors: Mestre Sanchis Antonio 
Published: April 2016

Pese a tantos estudios dedicados a nuestro siglo XVI, la actitud de los obispos españoles, en su intento de aplicar las disposiciones de Trento, no siempre es bien conocida. Constituye un simplismo facilón identificar a todos los que no encajan dentro de la línea erasmiana, calificándolos de contrarreformistas, sin distinguir matices ni precisar divergencias de criterio. De ahí que la contrarreforma haya sido uno de los conceptos más utilizados aunque, en muchos casos, haya servido para enmascarar la ignorancia de las verdaderas corrientes de pensamiento en la España del XVI. Y, como no podía ser menos, lo mismo ha ocurrido en el caso de la iglesia del Antiguo Reino en Valencia. Si ensayos más intuitivos que fundados en datos rigurosamente históricos parecían formar un bloque homogéneo al tratar de los obispos valencianos, estudios recientes han venido a demostrar que no siempre coincidieron en sus disposiciones disciplinares, ni en su visión de los problemas político-sociales, culturales e incluso religiosos.
Oligarquía municipal e intereses agrarios: Orihuela en la coyuntura subsiguiente a la peste de 1648
Authors: Bernabé Gil David 
Published: April 2016

El concepto de decadencia aplicado a la economía del Seiscientos requiere de una serie de matizaciones que, partiendo de estudios monográficos o de carácter comarcal, revelen o cuestionen en su justo término el significado real de dicho concepto. Conocer la dinámica interna de los grupos de poder municipales y sus comportamientos políticos y económicos resulta imprescindible para la justa comprensión del problema. Prescindiendo por el momento de realizar esta tarea de una manera exhaustiva, aquí se tratará de relacionar de alguna manera la situación de la agricultura en Orihuela y los problemas que de ella derivan con los intereses de la oligarquía local en los años subsiguientes a la epidemia de 1648. Esto es, en un momento coyuntural un tanto especial pero que, pese a sus graves connotaciones demográficas, más que constituir un corte brusco en la evolución de la centuria, ha de contemplarse como la culminación de un proceso donde llegan a explicarse de forma más intensa los problemas de fondo.
Las temporalidades de la Compañía de Jesús en Alicante (Siglos XVII-XVIII)
Authors: Alberola Romá Armando , Giménez López Enrique 
Published: April 2016

Han sido escasos los trabajos destinados a valorar el volumen de las temporalidades de la Compañía de Jesús en el momento de su expulsión en 1767. Tan sólo se han acometido aproximaciones parciales al problema, en especial destinadas a documentar el destino de los Colegios y casas de residencia que, en buena parte, fueron convertidos en seminarios diocesanos o destinados a centros de educación seglar. Sin embargo, el conjunto del patrimonio de la Compañía resulta desconocido, y aún más el proceso de su formación y el volumen de propiedad rústica y urbana que fue sacado al mercado para su venta tras la expulsión. Nuestro propósito es, precisamente, ocuparnos de esta parcela descuidada e importantísima del extrañamiento de los jesuitas en el ámbito de la ciudad de Alicante, localidad que contaba con uno de los 142 colegios y casas de residencia que se repartían por toda España.
El proceso repoblador tras la expulsión de los moriscos en el señorío de Relleu
Authors: Claver Cortés María del Carmen 
Published: April 2016

Extracto de la memoria de licenciatura dirigida por el Dr. Antonio Gil Olcina y presentada en la Universidad de Alicante (1982). En los últimos tiempos ha tenido lugar una eclosión de trabajos que centran su interés en la problemática de las tierras señoriales. En el ámbito valenciano, el régimen señorial alcanzó un gran desarrollo; todos los autores destacan la importancia, en base a la repercusión social y económica, del hecho de que hasta comienzos del s. XVIII y la disolución del régimen señorial, hay un predominio de las tierras egresadas de la Corona. La expulsión de los moriscos es un aspecto fundamental en la historia del País Valenciano. El Decreto de 9 de abril llevará implícito toda una serie de consecuencias, tanto en el aspecto social como en el económico. Relleu era un lugar de moriscos que quedó prácticamente despoblado tras la expulsión. En el presente artículo intentaremos analizar las repercusiones demográficas y sociales del Decreto en el lugar de Relleu.
Fuero alfonsino y fuero de población de Sierra Morena en los proyectos de colonización de la Corona de Aragón en la segunda mitad del siglo XVIII
Authors: Giménez López Enrique 
Published: April 2016

Si bien la paternidad de la Instrucción y Fuero de Población contenida en la Real Cédula de 5 de julio de 1767 sigue siendo debatida, nadie pone en duda el carácter modélico que se quiso dar a su articulado, tenido como síntesis del poblacionismo agrarista y guía de muchas de las empresas colonizadoras impulsadas durante la segunda mitad del Setecientos. Su referencia habitual, como veremos, en los proyectos y realizaciones de empresas colonizadoras impulsadas en los territorios de la antigua Corona de Aragón en ese mismo período prueba el carácter paradigmático del Fuero de Población, si bien en Valencia, sur de Cataluña, algunos lugares de Aragón y Mallorca, su preeminencia hubo de compartirla con el denominado Fuero Alfonsino, un poderoso instrumento repoblador utilizado desde el siglo XIV, hibernado desde 1707, y recuperado en sus potencialidades en la década de 1770.
The transformation of sacrifice theme in opera repertoire<p>Opera repertuvarında kurban temasının dönüşümü
Authors: Öğüt Evrim Hikmet 
Published: April 2016

The concept of sacrifice, with roots in pre-historic times, not only has sustained its primary meaning throughout the history but also has gained secondary meanings besides its ritual, religious and divine features. While various aspects of the concept can be found in the opera repertoire, the mentioned transformation can be traced particularly in the context of human sacrifice.In parallel with the transformation of opera repertoire from 18th to 20th centuries, this study, examining a selection of the opera repertoire with the concept of human sacrifice; with a chronological perspective, aims to present the new meanings of the concept of sacrifice and the act of human sacrifice have gained.Not covering a musicological analysis of the operas, this study aims to draw attention to the historical sense of and the dynamic character of the opera as well as, to the methods applied when dealing with the subject of human sacrifice, which is a tough and pre-modern subject in contrast to opera as a “modern” artistic form. Özetİnsanlık tarihiyle yaşıt olan kurban kavramı tarih öncesinden günümüze gelen süreç içinde birincil anlamını koruduğu gibi, ritüel boyutundan, dini ve kutsal boyutlardan sıyrılarak ikincil anlamlar kazanmıştır. Opera repertuvarı incelendiğinde kavramın pek çok farklı görünümünü bulmak mümkün olduğu gibi, söz edilen dönüşümü özellikle insan kurban etme bağlamında takip etmek mümkündür.Temel olarak, opera repertuvarında insan kurban edilmesini konu alan örneklerden bir seçme üzerinde duracak olan bu çalışma, kronolojik bir bakışla, kurban kavramının ve insan kurban etme düşüncesinin kazandığı yeni anlamları, opera anlayışının 18. yüzyıldan 20. yüzyıla gelen süreçte geçirdiği değişime paralel olarak sunmayı amaçlamaktadır.Çalışma, söz edilecek operalara ilişkin müzikbilimsel bir incelemeyi içermemekle birlikte, opera gibi çoksesli Batı müzik geleneğinin merkezinde yer alan ve “modern” olarak adlandırılabilecek olan bir türün, özellikle insan kurban edilmesi gibi zorlu ve modern-öncesi bir konuyu ele alırken baş vurduğu yöntemlere, operanın tarihselliğine ve dinamik karakterine dikkat çekmeyi amaçlamaktadır
Alive and kicking, or, living on borrowed time? – Microsatellite diversity in natural populations of the endangered Ulmus minor Mill. sensu latissimo from Croatia
Authors: Zebec Marko , Idžojtić Marilena , Šatović Zlatko , Poljak Igor , Liber Zlatko 
Published: April 2016

AbstractThe main objective of this research was to assess the genetic diversity of 5 natural field elm populations in Croatia. The study results suggest that the observed populations are characterized by a satisfactory amount of heterozygosity, and that the impact of the Dutch elm disease on the amount of genetic diversity in the sampled populations is currently negligible. However, one population displayed a significant excess of heterozygosity, implying a genetic bottleneck. The existence of a very clear genetic differentiation between the continental and the Mediterranean populations of Ulmus minor in Croatia was noticed.
Epilithic diatom assemblages and environmental quality of the Su Gologone karst spring (centraleastern Sardinia, Italy)
Authors: Lai Giuseppina G. , Padedda Bachisio M. , Wetzel Carlos E. , Lugliè Antonella , Sechi Nicola , Ector Luc 
Published: April 2016

AbstractKarst springs are considered among the most vulnerable groundwater-dependent ecosystems. Despite their ecological value and importance as strategic water sources, Mediterranean karst springs are still poorly investigated. The aim of this study was to analyse the epilithic diatom assemblages and to test their usefulness as indicators of environmental quality on the Su Gologone spring (central-eastern Sardinia, Italy), a biotope of great natural value and a precious source of drinking water. A total of 89 diatom taxa were found with 25 new records for Sardinian running waters. Species richness, Shannon-Wiener and Pielou indices showed good biotic integrity. The dominant taxa were alkaliphilous, halophobous-oligohalobous exigent, xeno- oligosaprobic and characteristic of oligotrophic waters. The eutrophication/pollution index − diatom based (EPI-D) and the Navicula Nitzschia Surirella indices indicated respectively an excellent/good biological water quality and a low physical disturbance. However, the biological and chemical oxygen demand, and the microbiological variables (E. coli, fecal and total coliforms) revealed an organic contamination of the water, although moderate. The judgment provided by the EPI-D should be verified after updating of the index. In fact, 10 taxa found in this study are not currently considered by the EPI-D method.
Impact of nickel on grapevine (Vitis vinifera L.) root plasma membrane, ROS generation, and cell viability
Authors: Pavlovkin Ján , Fiala Roderik , Čiamporová Milada , Martinka Michal , Repka Vladimír 
Published: April 2016

Abstract
The present study investigated the impact of nickel (Ni2+) on trans-membrane electrical potential (EM) and permeability properties of plasma membrane (PM) in epidermal cells of adventitious grapevine roots. The relationship between disturbances of membrane functionality and the production of superoxide anion, hydrogen peroxide and cell viability after the exposure of roots to Ni2+ was also studied. Treatments with 0.1-5 mmol L-1 NiCl2 induced a concentration-dependent transient PM depolarization, which was recovered to the initial resting potential within 50-70 min in the presence of Ni2+. Longer (up to 24 h) exposure of roots to 1 mmol L-1 of Ni2+ hyperpolarized the EM by approximately 17 mV. Application of the highest 5 mmol L-1 concentration of Ni2+ during longer treatments (up to 48 h) resulted in the increase of membrane permeability; however the EM, cell viability, and superoxide content remained unaffected. The increase in the formation of hydrogen peroxide was time- and concentration- dependent and maximum production was recorded after 180 min of Ni2+ treatment. We can conclude that oxidative stress resulting from an imbalance in the generation and/ or removal of hydrogen peroxide in the root tissues of grapevine was the major cause of Ni2+ toxicity.
A comparison of the influences of flotation and wet sieving on certain carbonized legume and cereal remains
Authors: Mareković Sara , Šoštarić Renata 
Published: April 2016

Abstract
In order to determine the influence of recovery techniques with water (flotation and wet sieving) on carbonized plant remains, a certain amount of wheat, barley, millet, horsebean and lentil macrofossils from archaeological sites was taken and treated with water. Moist recovery was also applied to in-laboratory, artificially, charred barley, millet and lentil samples. After the treatments, the investigated remains were re-counted and the percentages of still recognizable remains for every plant species and for each method were recorded. Comparisons were made of the sensitivities of the investigated species and of the differences in the degree of macrofossil breakup depending on the method of recovery. Our investigation proved that flotation is a less aggressive method than wet sieving and that barley, horsebean and wheat carbonized macrofossils are resistant to moist treatments, while the breakup percentage of lentil and millet (from archaeological sites) is higher than 30%, which should be taken into account when deciding on the (non)use of water recovery in the investigations.
Development of a System Dynamics Model for Evaluation of the Impact of Integration of Renewable Energy Sources on the Operational Efficiency of Energy Supply Facilities: Theoretical Background
Authors: Balodis Māris , Skribans Valērijs , Ivanova Poļina 
Published: April 2016

Abstract
Nowadays, energy companies operate in a highly competitive environment. To maintain the leader position, as a reaction to various changes energy companies must take appropriate steps in a timely manner.
Correct assessment of the situation ensures implementation of adequate measures. The situation can be assessed correctly by using a complex approach and/or analysing it according to the specific circumstances. The complex approach also envisages designing of an appropriate model, which studies the impact of changes on the research object, while dealing with the object within a system and as part of the system.
The article gives a theoretical background of the system dynamics model in order to evaluate the impact of integration of renewable energy sources (RES) on the operational efficiency of energy supply facilities (power and heat supply) on the national and regional levels, as well as provides the first modelling results.