bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEK-independent ERK activation in human neutrophils and its impact on functional responses
Authors: Simard Francois A , Cloutier Alexandre , Ear Thornin , Vardhan Harsh , McDonald Patrick P 
Published: August 2015

Abstract
Neutrophils influence innate and adaptative immunity, notably through the generation of numerous cytokines and chemokines and through the modulation of their constitutive apoptosis. Several signaling cascades are known to control neutrophil responses, including the MEK pathway, which is normally coupled to ERK. However, we show here that in human neutrophils stimulated with cytokines or TLR ligands, MEK and ERK are activated independently of each other. Pharmacological blockade of MEK had no effect on the induction of ERK kinase activity and vice versa. In autologous PBMC exposed to the same stimuli or in neutrophils exposed to chemoattractants, this uncoupling of MEK and ERK was not observed. Whereas we had shown before that MEK inhibition impairs cytokine generation translationally in LPS- or TNF-stimulated neutrophils, ERK inhibition affected this response transcriptionally and translationally. Transcriptional targets or ERK include the mitogen- and stress-activated protein kinase 1 (MSK-1) and its substrates, C/EBPβ and CREB, whereas translational targets include the S6 kinase and its substrate, the S6 ribosomal protein. In addition to affecting cytokine production, ERK inhibition interfered with how LPS or TNF promotes neutrophil survival and levels of the myeloid cell leukemia 1 (Mcl-1) antiapoptotic protein. Whereas the ERK-activating kinase was not identified, we found that the MAP3K, TGF-β-activated kinase 1 (TAK1), acts upstream of ERK and MEK in neutrophils. Our results document a functional uncoupling of the MEK/ERK module under certain stimulatory conditions and suggest that therapeutic strategies based on MEK inhibition might benefit from being complemented by ERK inhibition, particularly in chronic inflammatory conditions featuring a strong neutrophilic component.
Preconditioning in the reef-building coralPocillopora damicornisand the potential for trans-generational acclimatization in coral larvae under future climate change conditions
Authors: Putnam Hollie M. , Gates Ruth D. 
Published: August 2015

ABSTRACTCoral reefs are globally threatened by climate change-related ocean warming and ocean acidification (OA). To date, slow-response mechanisms such as genetic adaptation have been considered the major determinant of coral reef persistence, with little consideration of rapid-response acclimatization mechanisms. These rapid mechanisms such as parental effects that can contribute to trans-generational acclimatization (e.g. epigenetics) have, however, been identified as important contributors to offspring response in other systems. We present the first evidence of parental effects in a cross-generational exposure to temperature and OA in reef-building corals. Here, we exposed adults to high (28.9°C, 805 µatm PCO2) or ambient (26.5°C, 417 µatm PCO2) temperature and OA treatments during the larval brooding period. Exposure to high treatment negatively affected adult performance, but their larvae exhibited size differences and metabolic acclimation when subsequently re-exposed, unlike larvae from parents exposed to ambient conditions. Understanding the innate capacity corals possess to respond to current and future climatic conditions is essential to reef protection and maintenance. Our results identify that parental effects may have an important role through (1) ameliorating the effects of stress through preconditioning and adaptive plasticity, and/or (2) amplifying the negative parental response through latent effects on future life stages. Whether the consequences of parental effects and the potential for trans-generational acclimatization are beneficial or maladaptive, our work identifies a critical need to expand currently proposed climate change outcomes for corals to further assess rapid response mechanisms that include non-genetic inheritance through parental contributions and classical epigenetic mechanisms.
Finding the shortest path with PesCa: a tool for network reconstruction
Authors: Scardoni Giovanni , Tosadori Gabriele , Pratap Sakshi , Spoto Fausto , Laudanna Carlo 
Published: August 2015

Network analysis is of growing interest in several fields ranging from economics to biology. Several methods have been developed to investigate different properties of physical networks abstracted as graphs, including quantification of specific topological properties, contextual data enrichment, simulation of pathway dynamics and visual representation. In this context, the PesCa app for the Cytoscape network analysis environment is specifically designed to help researchers infer and manipulate networks based on the shortest path principle. PesCa offers different algorithms allowing network reconstruction and analysis starting from a list of genes, proteins and in general a set of interconnected nodes. The app is useful in the early stage of network analysis, i.e. to create networks or generate clusters based on shortest path computation, but can also help further investigations and, in general, it is suitable for every situation requiring the connection of a set of nodes that apparently do not share links, such as isolated nodes in sub-networks. Overall, the plugin enhances the ability of discovering interesting and not obvious relations between high dimensional sets of interacting objects.
CySpanningTree: Minimal Spanning Tree computation in Cytoscape
Authors: Shaik Faizaan , Bezawada Srikanth , Goveas Neena 
Published: August 2015

Simulating graph models for real world networks is made easy using software tools like Cytoscape. In this paper, we present the open-source CySpanningTree app for Cytoscape that creates a minimal/maximal spanning tree network for a given Cytoscape network. CySpanningTree provides two historical ways for calculating a spanning tree: Prim’s and Kruskal’s algorithms. Minimal spanning tree discovery in a given graph is a fundamental problem with diverse applications like spanning tree network optimization protocol, cost effective design of various kinds of networks, approximation algorithm for some NP-hard problems, cluster analysis, reducing data storage in sequencing amino acids in a protein, etc. This article demonstrates the procedure for extraction of a spanning tree from complex data sets like gene expression data and world network. The article also provides an approximate solution to the traveling salesman problem with minimum spanning tree heuristic. CySpanningTree for Cytoscape 3 is available from the Cytoscape app store.
Robust Multiarmed Bandit Problems
Authors: Kim Michael Jong , Lim Andrew E.B. 
Published: August 2015

The multiarmed bandit problem is a popular framework for studying the exploration versus exploitation trade-off. Recent applications include dynamic assortment design, Internet advertising, dynamic pricing, and the control of queues. The standard mathematical formulation for a bandit problem makes the strong assumption that the decision maker has a full characterization of the joint distribution of the rewards, and that “arms” under this distribution are independent. These assumptions are not satisfied in many applications, and the out-of-sample performance of policies that optimize a misspecified model can be poor. Motivated by these concerns, we formulate a robust bandit problem in which a decision maker accounts for distrust in the nominal model by solving a worst-case problem against an adversary (“nature”) who has the ability to alter the underlying reward distribution and does so to minimize the decision maker’s expected total profit. Structural properties of the optimal worst-case policy are characterized by using the robust Bellman (dynamic programming) equation, and arms are shown to be no longer independent under nature’s worst-case response. One implication of this is that index policies are not optimal for the robust problem, and we propose, as an alternative, a robust version of the Gittins index. Performance bounds for the robust Gittins index are derived by using structural properties of the value function together with ideas from stochastic dynamic programming duality. We also investigate the performance of the robust Gittins index policy when applied to a Bayesian webpage design problem. In the presence of model misspecification, numerical experiments show that the robust Gittins index policy not only outperforms the classical Gittins index policy, but also substantially reduces the variability in the out-of-sample performance.This paper was accepted by Dimitris Bertsimas, optimization.
Primary standard for liquid flow rates between 30 and 1500 nl/min based on volume expansion
Authors: Lucas Peter , Ahrens Martin , Geršl Jan , Sparreboom Wouter , Lötters Joost 
Published: August 2015

AbstractAn increasing number of microfluidic systems operate at flow rates below 1 μl/min. Applications include (implanted) micropumps for drug delivery, liquid chromatography, and microreactors. For the applications where the absolute accuracy is important, a proper calibration is required. However, with standard calibration facilities, flow rate calibrations below ~1 μl/min are not feasible because of a too large calibration uncertainty. In the current research, a traceable flow rate using a certain temperature increase rate is proposed. When the fluid properties, starting mass, and temperature increase rate are known, this principle yields a direct link to SI units, which makes it a primary standard. In this article, it will be shown that this principle enables flow rate uncertainties in the order of 2–3% for flow rates from 30 to 1500 nl/min.
Effect of Activating Agent on the Preparation of Bamboo-Based High Surface Area Activated Carbon by Microwave Heating
Authors: Xia Hongying , Wu Jian , Srinivasakannan Chandrasekar , Peng Jinhui , Zhang Libo 
Published: August 2015

Abstract
The present work attempts to convert bamboo into a high surface area activated carbon via microwave heating. Different chemical activating agents such as KOH, NaOH, K2CO3 and Na2CO3 were utilized to identify a most suitable activating agent. Among the activating agents tested KOH was found to generate carbon with the highest porosity and surface area. The effect of KOH/C ratio on the porous nature of the activated carbon has been assessed. An optimal KOH/C ratio of 4 was identified, beyond which the surface area as well as the pore volume were found to decrease. At the optimized KOH/C ratio the surface area and the pore volume were estimated to be 3,441 m2/g and 2.093 ml/g, respectively, with the significant proportion of which being microporous (62.3%). Activated carbon prepared under the optimum conditions was further characterized using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). Activated carbons with so high surface area and pore volume are very rarely reported, which could be owed to the nature of the precursor and the optimal conditions of mixture ratio adopted in the present work.
Oxidizing Roasting Performances of Coke Fines Bearing Brazilian Specularite Pellets
Authors: Chun Tiejun , Zhu Deqing 
Published: August 2015

Abstract
Oxidized pellets, consisting of Brazilian specularite fines and coke fines, were prepared by disc pelletizer using bentonite as binder. The roasting process of pellets includes preheating stage and firing stage. The compressive strength of preheated pellets and fired pellets reached the peak value at 1.5% coke fines dosage. During the initial stage of preheating, some original Fe2O3 was reduced to Fe3O4 because of partial reduction atmosphere in pellet. During the later stage of preheating and firing stage, coke fines were burnt out, and the secondary Fe2O3 (new generation Fe2O3) was generated due to the re-oxidization of Fe3O4, which improved the recrystallization of Fe2O3. Compared with the fired pellets without adding coke fines, fired pellets with 1.5% coke fines exhibited the comparable RSI (reduction swelling index) and RDI+3.15 mm (reduction degradation index), and slightly lower RI (reducibility index).
Thyrotropin-secreting pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglandular syndrome
Authors: Mazerkina Nadia , Trunin Yuri , Gorelyshev Sergey , Golanov Andrey , Kadashev Boris , Shishkina Liudmila , Rotin Daniil , Karmanov Maxim , Orlova Elizabet 
Published: August 2015

AbstractThyrotropinomas (TSHomas) are rare pituitary adenomas, particularly in childhood. We present here the case of an 11-year-old boy with type 1 autoimmune polyglandular syndrome (APS1) and TSHoma which was diagnosed by elevated thyroid – stimulating hormone and thyroid hormones levels without evident clinical signs of hyperthyroidism. He was underwent partial resection of the tumor via transsphenoidal approach and subsequently radiation therapy. Consequently, 1 year after radiotherapy, the patient developed growth hormone deficiency, three and half years after radiation became euthyroid, and five and half years after treatment – hypothyroid. This is the first case of the coexistence of these two rare endocrine diseases in one patient.
Levothyroxine replacement in primary congenital hypothyroidism: the higher the initial dose the higher the rate of overtreatment
Authors: Tuhan Hale , Abaci Ayhan , Cicek Gizem , Anik Ahmet , Catli Gonul , Demir Korcan , Bober Ece 
Published: August 2015

AbstractCongenital hypothyroidism (CH) is the most frequent endocrine disorder during the neonatal period, and a delay in diagnosis and treatment leads to irreversible complications. A high L-thyroxine (LT4) dose is recommended for treatment, while the optimal starting dose is still a matter of debate. The objective of this study was to determine the effects of various starting doses of LT4 on serum thyroid stimulating hormone (TSH) and thyroxine (fT4) at the end of the first month of treatment.A total of 71 patients (37 males, 52.1%) with CH were included in the study. The patients were designated into three sets of subgroups according to the following categorical variables: (i)The mean age of the study population was 22.3±13.2 days at diagnosis. At diagnosis, the mean fT4 was 0.84±0.32 ng/dL, and TSH was 39.3±30 μIU/mL. The mean initial dose of LT4 was 10.9±2.9 μg/kg/day. Overtreatment rates were significantly higher in the highest dose group (12–17 μg/kg/day) compared with the lowest dose group (6–9.9 μg/kg/day) (61.5% and 25%, respectively, p<0.05). None of the patients was undertreated.In this study, we found that the rate of overtreatment was significantly higher in patients who were given LT4 doses of 12–17 μg/kg/day. Thus, monitoring thyroid functions earlier than one month of treatment is necessary.
The 10 Hounsfield units unenhanced computed tomography attenuation threshold does not apply to cortisol secreting adrenocortical adenomas
Authors: Chambre Claire , McMurray Emily , Baudry Camille , Lataud Marine , Guignat Laurence , Gaujoux Sébastien , Lahlou Najiba , Guibourdenche Jean , Tissier Frédérique , Sibony Mathilde , Dousset Bertrand , Bertagna Xavier , Bertherat Jérôme , Legmann Paul , Groussin Lionel 
Published: August 2015

ContextComputed tomography (CT) unenhanced attenuation value of <10 Hounsfield units (HU) has an excellent specificity (98%) to diagnose lipid-rich adrenocortical adenomas (ACAs) with a weaker sensitivity (71%).ObjectiveTo determine from a routine clinical perspective if unenhanced attenuation value is influenced by cortisol secretion in ACAs.DesignThis was a retrospective study of cases collected between 2009 and 2012.SettingThis study was conducted in a tertiary-care university hospital.PatientsSeventy-two patients operated on for an ACA (Weiss score ≤2) were analysed. Thirty-four patients had an ACA oversecreting cortisol (Cush-ACA). Thirty-eight patients had an ACA without cortisol oversecretion (Non Hyper-ACA).Main outcome measureCT unenhanced attenuation value was correlated with the functional status. The Weiss score items were analysed.ResultsAmong the 34 patients with a Cush-ACA a minority (n=7) had an unenhanced attenuation value under 10 HU. Among the high precontrast density (>10 HU) Cush-ACAs, washout analysis after contrast administration was consistent with the benign nature of the tumor in ∼60% of the cases. Less than 25% clear cells (lipid-rich cells), a Weiss score item, was present in 50% of the Cush-ACAs in favour of a lipid-poor content.ConclusionsUnenhanced attenuation value has a poor sensitivity to diagnose an ACA in case of cortisol oversecretion due to poor lipid content. Nevertheless, the accuracy of washout analysis was preserved in the group of Cush-ACAs.
Pegvisomant in combination with long-acting somatostatin analogues in acromegaly: the role of the GH receptor deletion of exon 3
Authors: Franck S E , van der Lely A J , Delhanty P J D , Jørgensen J O L , Neggers S J C M M 
Published: August 2015

BackgroundDoses of the GH receptor (GHR) antagonist pegvisomant (PEGV) that normalize insulin-like growth factor 1 (IGF1) levels vary widely among acromegaly patients. Predictors for PEGV response are baseline IGF1 levels, sex, body weight and previous radiotherapy. A GHR polymorphism lacking exon 3 (d3-GHR) is frequent in the general population. The influence of d3-GHR on PEGV responsiveness in acromegaly is unclear.ObjectiveTo assess the influence of d3-GHR on IGF1 levels and PEGV responsiveness in acromegaly patients using combined PEGV and long-acting somatostatin receptor ligand (LA-SRIF) treatment.DesignData were collected at the Rotterdam Pituitary Centre between 2004 and 2013. Patients with elevated IGF1 levels (>1.2 upper limit of normal;n=112) and over 6 months of high-dose LA-SRIF treatment were co-treated with PEGV. GHR genotype was assessed using genomic DNA in 104 patients.ResultsD3-GHR was observed in 51 (49.0%) of the patients (7.7% homozygous, 41.3% heterozygous) and was in Hardy–Weinberg equilibrium (P=0.859). Baseline characteristics were similar in d3-GHR and full-length (fl)-GHR genotypes. During PEGV/LA-SRIF treatment IGF1 levels were not different between d3-carriers and non-carriers. Similarly, no difference in PEGV dose required to normalize IGF1 (P=0.337) or PEGV serum levels (P=0.433) was observed between the two groups. However, adenoma size decreased significantly (>20% of largest diameter) in 25.6% of the fl-GHR genotype but only in 7.5% of d3-carriers (P=0.034, OR: 4.6 (CI: 1.1–18.9)).ConclusionsGHR genotype does not predict the IGF1 normalizing dose of PEGV in acromegaly patients using combination PEGV/LA-SRIF treatment. However, fewer d3-carriers showed significant reductions in adenoma size.
Referral bias in female functional hyperandrogenism and polycystic ovary syndrome
Authors: Luque-Ramírez Manuel , Alpañés Macarena , Sanchón Raul , Fernández-Durán Elena , Ortiz-Flores Andrés E , Escobar-Morreale Héctor F 
Published: August 2015

ObjectiveWomen with polycystic ovary syndrome (PCOS) seeking health care in the United States may be more obese and hyperandrogenic than those present in the general population. We aimed to assess the impact of referral bias on European women with functional androgen excess disorders.DesignCross-sectional study.MethodsWe studied two groups of patients: i) 368 consecutive patients referred to our clinic for the study of functional hyperandrogenism (FH) (referral patients); ii) 57 consecutive premenopausal patients identified by screening during blood donation (unselected patients). We compared the anthropometric data from the groups of patients with those of two control populations: iii) a group of unselected premenopausal healthy female blood donors (unselected controls); and iv) data available from the local general premenopausal female population.ResultsReferral patients with FH were more hirsute, had a higher percentage of hyperandrogenemia, and fulfilled PCOS criteria more frequently than unselected patients. The prevalence of obesity in unselected controls was similar to that observed in the general population, whereas referral patients and unselected patients were more frequently obese. The prevalence of obesity was also higher among referral patients compared to unselected patients.ConclusionReferral bias influences the phenotype of patients with FH. Patients studied at the clinical setting may show more severe hyperandrogenic and obese phenotypes than patients from the general population, even though PCOS appears to be associated with weight excess also in the general European population. This fact should be considered when establishing reference values and control populations for clinical and research purposes.
Monitoring ground subsidence in urban environments: M-30 tunnels under Madrid City (Spain)
Authors: Martínez Marín Rubén , Sillerico Eleanor , Ezquerro Pablo , Marchamalo Miguel , Herrera Gerardo , Duro Javier 
Published: August 2015

Big cities improvement usually requires the construction of large underground infrastructures, in order to ensure proper communication and optimize urban use. Monitoring ground subsidences is therefore one of the main challenges in changing urban environments. The "Madrid Río" project (2003-2008) is an effort to reclaim the riverfront land and improve the busy M-30 beltway that involved the construction of 7.93 km of tunnels underneath the southern center of Madrid City. This paper presents a remote-sensing approach to monitor ground subsidences induced by tunneling excavation. The Persistent Scatterers Interferometry technique (PSI) was used to estimate subsidence and displacement time series from Synthetic Aperture Radar images, acquired between August 2003 and April 2008 from ENVISAT. Remote sensed results were compared to traditional extensometric measures, fitting adequately for selected sectors. Spatial analysis of displacements allowed evaluating impacts of tunneling on surrounding buildings and facilities, highlighting critical areas. The availability of a spatial distribution of displacements in a time series allowed analyzing longitudinal, cross-sectional and temporal dynamics. The main limitations during this work were the heterogeneous spatial distribution of Persistent Scatterers, the absence of measurement points in work areas, the threshold for velocity detection and low temporal resolution of ENVISAT images. Nevertheless, these limitations of DInSAR for monitoring infrastructures are overcome by actual satellites, being a complementary technique with an exceptional added value and temporal analysis capability.