bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding off‐targets, biological pathways, and target diseases for chymase inhibitors via structure‐based systems biology approach
Authors: Arooj Mahreen , Sakkiah Sugunadevi , Cao Guang Ping , Kim Songmi , Arulalapperumal Venkatesh , Lee Keun Woo 
Published: August 2014

ABSTRACTOff‐target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off‐targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off‐target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off‐targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off‐targets into biological pathways and to establish links between pathways and particular adverse effects. Off‐targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off‐targets. These off‐targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. Proteins 2015; 83:1209–1224. © 2014 Wiley Periodicals, Inc.
Regulation of Mitochondrial Function and Cellular Energy Metabolism by Protein Kinase C-λ/ι: A Novel Mode of Balancing Pluripotency
Authors: Mahato Biraj , Home Pratik , Rajendran Ganeshkumar , Paul Arindam , Saha Biswarup , Ganguly Avishek , Ray Soma , Roy Nairita , Swerdlow Russell H. , Paul Soumen 
Published: August 2014

Abstract
Pluripotent stem cells (PSCs) contain functionally immature mitochondria and rely upon high rates of glycolysis for their energy requirements. Thus, altered mitochondrial function and promotion of aerobic glycolysis are key to maintain and induce pluripotency. However, signaling mechanisms that regulate mitochondrial function and reprogram metabolic preferences in self-renewing versus differentiated PSC populations are poorly understood. Here, using murine embryonic stem cells (ESCs) as a model system, we demonstrate that atypical protein kinase C isoform, PKC lambda/iota (PKCλ/ι), is a key regulator of mitochondrial function in ESCs. Depletion of PKCλ/ι in ESCs maintains their pluripotent state as evident from germline offsprings. Interestingly, loss of PKCλ/ι in ESCs leads to impairment in mitochondrial maturation, organization, and a metabolic shift toward glycolysis under differentiating condition. Our mechanistic analyses indicate that a PKCλ/ι-hypoxia-inducible factor 1α-PGC1α axis regulates mitochondrial respiration and balances pluripotency in ESCs. We propose that PKCλ/ι could be a crucial regulator of mitochondrial function and energy metabolism in stem cells and other cellular contexts. Stem Cells 2014;32:2880–2892
Application of a Three‐dimensional Print of a Liver in Hepatectomy for Small Tumors Invisible by Intraoperative Ultrasonography: Preliminary Experience
Authors: Igami Tsuyoshi , Nakamura Yoshihiko , Hirose Tomoaki , Ebata Tomoki , Yokoyama Yukihiro , Sugawara Gen , Mizuno Takashi , Mori Kensaku , Nagino Masato 
Published: August 2014

AbstractBackgroundHepatectomy for an invisible small tumor using intraoperative ultrasonography requires technical ingenuity. We used a 3D print of a liver to perform a hepatectomy on two patients with synchronous multiple liver metastases from colorectal cancer. Because of preoperative chemotherapy, one of the tumors became smaller and invisible to ultrasonography in each case. We present our procedure here.MethodsMultidetector‐row computed tomography images of anatomical structures were digitally segmented using the original software “PLUTO,” which was developed at the Graduate School of Information Science, Nagoya University. After converting the final segmentation data to stereolithography files, a 3D printed liver at a 70 % scale was produced. The support material was washed and the mold charge was removed from the 3D‐printed hepatic veins. The surface of the 3D‐printed model was abraded and coated with urethane resin paint. After air‐drying, the 3D‐printed hepatic veins were colored by injecting a dye. The 3D printed portal veins were whitish because mold charge remained. All procedures after 3D printing were performed by hand.ResultsHepatectomy for the small tumor that is invisible to intraoperative ultrasonography was performed by referring to a 3D‐printed model. The planned resections were successful with histologically negative surgical margins.ConclusionsThe application of a 3D‐printed liver to perform a hepatectomy for a small tumor that is invisible to intraoperative ultrasonography is an easy and feasible procedure. Use of 3D‐printing technology in hepatectomy requires further improvement and automation of hand work after the 3D print has been made.
Minimally Invasive Esophagectomy for Dysplastic Barrett’s Esophagus
Authors: Markar Sheraz R. , Hanna George 
Published: August 2014

AbstractA substantial portion of patients diagnosed preoperatively with high grade dysplasia (HGD) alone will have occult esophageal adenocarcinoma on analysis of the surgical specimen. Therefore, because of an increased risk of disease progression and malignancy, patients with HGD should be referred for esophagectomy promptly when endoscopic therapy has failed. The required extent of lymphadenectomy in this cohort of patients is unknown because of the variable incidence of submucosal cancer observed. Improvements in perioperative care, adoption of a minimally invasive surgical approach, and centralization of esophageal cancer services have substantially reduced the rates of mortality and morbidity associated with esophagectomy in recent years. Minimally invasive esophagectomy should be considered the treatment of choice in patients with dysplastic Barrett’s esophagus that is refractory to endoscopic therapy or those at high risk of invasive cancer.
A Proposed Matrix for Planning Global Surgery Interventions
Authors: Kushner Adam L. 
Published: August 2014

AbstractThe concept of surgery and global health is gaining acceptance; however, a great deal of confusion still exists as to what constitutes global surgery. To facilitate the overall view of how surgical care in a low resource setting can be integrated into a health system, a matrix for planning global surgery interventions has been developed. The key components of this tool are treatment locations and disease time course. The matrix also allows for the inclusion of information on surgical capacity for personnel, infrastructure, procedure, equipment, and supplies. This simple tool can assist researchers, program implementers, policy makers, and donors understand how to improve the delivery of surgical care to the billions of people around the world in need.
Measurement Biases Explain Discrepancies between the Observed and Simulated Decadal Variability of Surface Incident Solar Radiation
Authors: Wang Kaicun 
Published: August 2014

AbstractObservations have reported a widespread dimming of surface incident solar radiation (Rs) from the 1950s to the 1980s and a brightening afterwards. However, none of the state-of-the-art earth system models, including those from the Coupled Model Intercomparison Project phase 5 (CMIP5), could successfully reproduce the dimming/brightening rates over China. We find that the decadal variability of observed Rs may have important errors due to instrument sensitivity drifting and instrument replacement. While sunshine duration (SunDu), which is a robust measurement related to Rs, is nearly free from these problems. We estimate Rs from SunDu with a method calibrated by the observed Rs at each station. SunDu-derived Rs declined over China by −2.8 (with a 95% confidence interval of −1.9 to −3.7) W m−2 per decade from 1960 to 1989, while the observed Rs declined by −8.5 (with a 95% confidence interval of −7.3 to −9.8) W m−2 per decade. The former trend was duplicated by some high-quality CMIP5 models, but none reproduced the latter trend.
Wideband superconducting diplexer with stepped‐impedance cross‐structure
Authors: Lu Xilong , Guo Xubo , Cao Bisong , Wei Bin , Zhang Xiaoping 
Published: August 2014

A stepped‐impedance cross‐structure (SICS), consisting of a centre rectangular patch loaded with two pairs of stubs, is proposed for the designing of a wideband superconducting diplexer. Each pair of the stubs is designed for one channel of the diplexer, and is coupled by the centre rectangular patch with a strong coupling property required by the wide bandwidths. The frequencies and the coupling strengths of the two pairs of the stubs can be controlled independently. A superconducting diplexer has been successfully designed and fabricated with the proposed structure. The two channels are centred at 2.9 and 5.8 GHz with fractional bandwidths of 26.9 and 24.5%. The measured results of the fabricated device show low insertion losses and high isolations and agree well with the simulated ones.
Comparison of total energy expenditure assessed by two devices in controlled and free‐living conditions
Authors: Rousset Sylvie , Fardet Anthony , Lacomme Philippe , Normand Sylvie , Montaurier Christophe , Boirie Yves , Morio Béatrice 
Published: August 2014

AbstractThe objective of this study was to evaluate the validity of total energy expenditure (TEE) provided by Actiheart® and Armband®. Normal‐weight adult volunteers wore both devices either for 17 hours in a calorimetric chamber (CC, n = 49) or for 10 days in free‐living conditions (FLC) outside the laboratory (n = 41). The two devices and indirect calorimetry or doubly labelled water, respectively, were used to estimate TEE in the CC group and FLC group. In the CC, the relative value of TEE error was not significant (p > 0.05) for Actiheart® but significantly different from zero for Armband®, showing TEE underestimation (−4.9%, p < 0.0001). However, the mean absolute values of errors were significantly different between Actiheart® and Armband®: 8.6% and 6.7%, respectively (p = 0.05). Armband® was more accurate for estimating TEE during sleeping, rest, recovery periods and sitting–standing. Actiheart® provided better estimation during step and walking. In FLC, no significant error in relative value was detected. Nevertheless, Armband® produced smaller errors in absolute value than Actiheart® (8.6% vs. 12.8%). The distributions of differences were more scattered around the means, suggesting a higher inter‐individual variability in TEE estimated by Actiheart® than by Armband®. Our results show that both monitors are appropriate for estimating TEE. Armband® is more effective than Actiheart® at the individual level for daily light‐intensity activities.
Person endings in the old Italian verb system
Authors: Vanelli Laura 
Published: August 2014

AbstractThis chapter offers a contrastive account of the systems of verbal inflection in thirteenth-century Florentine (also known as old Italian) and in the modern language. The old Italian system is characterized, in particular, a) by a high degree of allotropy, that is to say of alternant realizations of the same cell in the paradigm, and b) by the nature of the endings in which we find those which are etymologically to be expected co-existing with the innovations which will in due course yield the modern system. The analysis of the old Italian system thus allows us to investigate the mechanisms and dynamics of morphological change by which one system has given way to the other. Of central importance here is the interaction of the principles of isomorphism and iconicity in determining the eventual outcome of the changing system
Kind-defining relative clauses in the diachrony of Italian
Authors: Beninca Paola , Cinque Guglielmo 
Published: August 2014

AbstractWithin the larger class of relative clauses, we isolate the subclass of relative clauses which modify a nominal predicate, as in Gianni è un uomo che non si dà mai per vinto (It.), ‘Gianni is a man that never surrenders’. This type of relative clause is shown to belong to a larger class of kind-defining relatives, in which other kinds of verbs incorporate a stage-level predicate. Their properties in varieties of Italian and English, and their evolution in the history of Italian are considered. Comparing old Florentine with other medieval and modern Italian varieties, it is clear that the diachronic change is very limited; the distinctive features that set this class apart are present in all of these linguistic areas. It is proposed their special properties can be related to the fact that, in opposition to restrictives, the DP in predicate position is not truly referential.
Looking Forward: Njal’s Prescience: Chapters 22–3
Authors: Miller William Ian 
Published: August 2014

Abstract
What of a strange chapter narrated in the future tense? This chapter is a discussion of the limits of Njal’s prescience and the constraints on it, which are quite substantial, his so-called prescience being more often what we would call sophistication regarding human behaviour. Njal also scripts some of his predictions; he does not read the future so much as make it. The discussion distinguishes among advice giving, prediction, persuasion, and prophecy, all of which readily use the future tense to tell ‘stories’ yet to happen. The role of Fate in the saga and in the literature on the sagas is criticized, and there is some discussion of the interpretive problems that arise, depending on the level of foreknowledge we attribute to Njal.
The Burning: Chapters 124–32
Authors: Miller William Ian 
Published: August 2014

Abstract
What are Njal’s motives in counselling to defend from inside the farmhouse? Skarphedin knows that it is lethal counsel, yet her defers, being intent on not marring his final scene by squabbling with his father. The chapter discusses in detail the sublime realization of the Burning: the triple meaning of Njal’s taking to his bed to die, Skarphedin’s launching of Kari, and the contrasting ‘miracles’ of Njal’s radiant corpse and Skarphedin’s never going down without lower legs and feet to stand on. It also discusses the complex character of Flosi, his losing a game of ‘chicken’ with Ingjald of Keldur. There is a formal farewell and evaluation of Skarphedin, his inability to escape his father’s control, and his ironical coming into his inheritance only as he and it are burning around him.
The Trial of Flosi and the Battle: Chapters 135, 141–5
Authors: Miller William Ian 
Published: August 2014

Abstract
This chapter deals extensively with the saga’s treatment of law, the limits of law, some procedural matters that may trouble the reader, the nature of legal expertise, and the portraits of three men of law: the wonderful Thorhall Asgrimsson, Mord, and Eyjolf, and their roles prior to and during the Battle at the Althing. It has been an unfortunate common critical response to read the saga as an indictment of the law. That is far from the case. The law functions well within appropriate limits, but the core feud of the saga comes to expand to something approaching law, and then is simply beyond the law’s competence, any law’s. The saga gives a remarkable astute analysis of just where the limits of law’s competence lie.
A Conclusion: Justice and Exits
Authors: Miller William Ian 
Published: August 2014

Abstract
A discussion of some troubling exits and non-exits of characters: primarily Mord and Hallgerd. Why is the latter just forgotten and dropped without a thought; why does the former suffer no sanction for his putative ill-doings? The writer is too given to realism and refusing easy moralizing. People like Mord tend to land on their feet because at some level they know their limits. Hallgerd’s revenge is appreciated for its utter non-utility, it being purely aesthetic, artfully accomplished, the moral and the aesthetic merging in refusal not to pay back what she owes. The sublimity of the author/narrator’s first person pronoun farewell is evoked.
Hindu Theology in Early Modern South Asia
Authors: Okita Kiyokazu 
Published: August 2014

Abstract
Focusing on the idea of genealogical affiliation (sampradāya), this book explores the interactions between royal power and priestly authority in eighteenth-century north India. Specifically, it examines how the religious policies of Jaisingh II (1688–1743) of Jaipur influenced the self-representation of Gauḍīya Vaiṣṇavas, as articulated by Baladeva Vidyābhūṣaṇa (c.1700–1793). Gauḍīya Vaiṣṇavas centred around the God Kṛṣṇa was initiated by Caitanya (1486–1533) and quickly became one of the most influential Hindu devotional movements in early modern South Asia. In the increasingly volatile late Mughal period, Jaisingh II tried to establish the legitimacy of his kingship by resorting to moral discourse. As a part of this strategy, he demanded that religious traditions in his kingdom conform to what he conceived of as Brahmanically normative. In this context the Gauḍīya school was forced to deal with their lack of clear genealogical affiliation, lack of an independent commentary on the Brahmasūtras, and their worship of Goddess Rādhā and Kṛṣṇa, who, according to the Gauḍīya, were not married. Based on a study of Baladeva’s Brahmasūtra commentary, the book examines how the Gauḍīya responded to the king’s demand, and thereby contributes to (1) genealogical studies; (2) the study of early modern South Asia; (3) Purāṇic studies, and (4) the study of Hindu theology.
The Learned Press: Oriental Languages
Authors: Hamilton Alastair 
Published: August 2014

Abstract
The publications of the Oxford press indicate the growing interest in Eastern languages from the sixteenth through the eighteenth centuries. The earliest publications were in the biblical languages Hebrew and Aramaic, for the study of Hebrew had become an essential part of the humanist tradition in England and two works of Hebrew grammar were published in the 1630s. Even before William Laud established a professorship of Arabic at the university, he acquired oriental types from Holland so that the press collection grew to include Arabic, Syriac, Ethiopic, Coptic, Armenian, Samaritan, and Cyrillic. While composing and proofing in these languages was laborious and expensive, print runs remained small and sales were seldom satisfactory. The Press nevertheless maintained consistently high standards of production and continued to advance oriental studies by supporting important new critical scholarship and commentary.
Maximum likelihood methods
Authors: Yang Ziheng 
Published: August 2014

AbstractThis chapter describes the pruning algorithm for calculating the likelihood on a tree, as well as extensions under complex substitution models, including the gamma and covarion models of rate variation among sites and lineages. It discusses numerical optimization algorithms for maximum likelihood estimation. It provides a critical assessment of methods for reconstructing ancestral states for both molecular sequences and morphological characters. Finally the chapter discusses model selection in phylogenetics using the likelihood ratio test (LRT) and information criteria such as the Akaike information criterion (AIC) and Bayesian information criterion (BIC).
Comparison of phylogenetic methods and tests on trees
Authors: Yang Ziheng 
Published: August 2014

AbstractThis chapter summarizes the criteria for comparing different tree reconstruction methods, such as consistency and efficiency, as well as computer simulation studies that evaluate the statistical performance of the various methods. It provides a critical examination of the assumptions underlying the parsimony method of phylogeny reconstruction, and its relationships to the likelihood method. It also discusses the differences of the maximum likelihood (ML) method for phylogeny reconstruction from conventional ML for parameter estimation and demonstrates that the ML tree does not have the asymptotic efficiency of a conventional likelihood estimate (MLE). The chapter then discusses the various statistical tests in the Frequentist framework developed to evaluate the significance of the estimated phylogenetic tree, including the bootstrap, K-H test, S-H test, etc..
Molecular clock and estimation of species divergence times
Authors: Yang Ziheng 
Published: August 2014

AbstractThis chapter discusses the hypothesis of the molecular clock and its use to date species divergences. It introduces various tests of the molecular clock as well as strategies to relax the clock in divergence time estimation. Bayesian methods of divergence time estimation are discussed in detail, including different prior models of rate drift such as the correlated-rate model based on the geometric Brownian motion process, and specification of the prior on divergence times incorporating uncertainties in fossil calibrations. The chapter describes the infinite-site and finite-site theories, which characterize the uncertainties in posterior divergence time estimates.
Quantitative genetic approaches to understanding sexual selection and mating system evolution in the wild
Authors: Reid Jane M. 
Published: August 2014

Abstract
Major ambitions in evolutionary biology are to understand the forces that drive the evolution and persistence of mate choice, and of associated primary and secondary sexual traits and emergent mating systems. Particular uncertainty, and hence substantial research interest, concerns the degree to which ongoing evolution of diverse morphological, physiological and behavioural traits and mating systems could be caused or constrained by indirect selection stemming from genetic covariation between such traits and associated mating preferences and fitness components. This chapter highlights the virtues of a quantitative genetic approach to answering such questions, in terms of both deriving pertinent theory and explicitly testing such theory in wild populations experiencing natural genetic and environmental variation. Two case studies are used, which aim to dissect the coevolution of a female mating preference and ornamental male trait in collared flycatchers (Ficedula albicollis) and the evolution of female extra-pair reproduction in song sparrows (Melospiza melodia), to illustrate the opportunities afforded by a wild population quantitative genetic approach to understanding sexual selection and mating system evolution, but also to illustrate the substantial remaining challenges.