bluuebunny/crossref_metadata_2025_split huggingface dataset:
To treat or not to treat – Successful hepatitis C virus eradication in a patient with advanced hepatocellular carcinoma and complete response to sorafenib
Authors: Waidmann Oliver , Peveling-Oberhag Jan , Eichler Katrin , Schulze Falko , Vermehren Johannes 
Published: November 2016

Abstract
Background and aims Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Infection with the hepatitis C virus (HCV) is one of the most frequent underlying diseases leading to HCC development. Sorafenib is the standard of care for HCC patients not amenable to local treatment, resection, or liver transplantation. Although overall survival can be increased, objective response rates in patients treated with sorafenib are low. In HCC patients who underwent resection or ablation, HCV eradication with interferon-based regimens reduces the risk of recurrence. However, it is not known and under strong debate if patients with HCC should be treated with interferon-free regimens. Furthermore, it is not known if patients with advanced HCC at the time of diagnosis should be treated with antiviral therapy.
Methods A patient with histologically confirmed advanced-stage HCC due to HCV-related cirrhosis was treated with sorafenib according to current guideline recommendations. Furthermore, he received subsequent treatment with direct antiviral agents (DAAs).
Results The patient achieved a complete response after sorafenib treatment was initiated. Sorafenib treatment was terminated 1 year after complete response. As no recurrence of HCC was evident after treatment cessation, antiviral treatment was initiated with paritaprevir/ritonavir, ombitasvir, dasabuvir, and dose-reduced ribavirin because of chronic kidney disease. The patient achieved a sustained viral response.
Conclusions Complete response to sorafenib treatment is scarce. Antiviral treatment should be considered in such patients as well as in patients with HCC who underwent resection or ablation.
Structural and functional consequences of a disease mutation in the telomere protein TPP1
Authors: Bisht Kamlesh , Smith Eric M. , Tesmer Valerie M. , Nandakumar Jayakrishnan 
Published: November 2016

Significance
Telomerase is an enzyme that replicates chromosome ends to facilitate continued stem cell division. Mutations in telomerase or in telomerase-related genes result in stem cell-dysfunction diseases, such as dyskeratosis congenita (DC). Despite its devastating nature, DC currently has no cure. Here we report the crystal structure of a mutant protein implicated in DC to reveal how the mutation disrupts a region of the protein essential for telomerase function. Furthermore, we demonstrated that this mutation, when introduced into a human cell line, is sufficient to cause the cellular underpinnings of DC. Our results therefore make the strong prediction that correcting the mutation in the stem cells of the patient will reverse the cellular symptoms of disease.
Rapid and independent memory formation in the parietal cortex
Authors: Brodt Svenja , Pöhlchen Dorothee , Flanagin Virginia L. , Glasauer Stefan , Gais Steffen , Schönauer Monika 
Published: November 2016

Significance
When it comes to memory, our brain needs to deal with two opposing demands: remaining plastic to acquire new information rapidly and maintaining old information faithfully over long periods. It is assumed that two distinct brain systems are in charge of these functions: the fast-learning hippocampus and the slow-learning neocortex. The interaction between these two systems has traditionally been seen as very slow, requiring weeks or months to build a neocortical memory trace. In this study, brain activity during virtual-reality navigation shows that contributions of hippocampus and parietal neocortex to memory are changing substantially already at the time a spatial memory representation is built. Notably, we show that the posterior parietal cortex fulfills all criteria for a hippocampus-independent memory representation.
Serotonin and arginine–vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain
Authors: Terranova Joseph I. , Song Zhimin , Larkin Tony E. , Hardcastle Nathan , Norvelle Alisa , Riaz Ansa , Albers H. Elliott 
Published: November 2016

SignificanceThere are profound sex differences in the expression of social behavior and in the incidence of many psychiatric disorders, and yet little is known about how the brain mechanisms underlying these phenomena differ in females and males. Here, we report that serotonin (5-HT) and arginine–vasopressin (AVP) act in opposite ways within the hypothalamus to regulate dominance and aggression in females and males. Dominance and aggression are promoted by 5-HT in females and by AVP in males. Because dominance and aggressiveness have been linked to the resistance to stress-related psychiatric disorders, these disorders may be more effectively treated with 5-HT–targeted drugs in females and AVP-targeted drugs in males.
Optimizing countershading camouflage
Authors: Cuthill Innes C. , Sanghera N. Simon , Penacchio Olivier , Lovell Paul George , Ruxton Graeme D. , Harris Julie M. 
Published: November 2016

SignificanceBecause the sun and sky are above us, natural illumination is directional and the cues from shading reveal shape and depth. However, many animals are darker on their backs and, over 100 years ago, it was proposed that this phenomenon was camouflage: countering the cues to shape that directional illumination creates. However, does this camouflage work in practice? We predicted the optimal countershading for different lighting conditions and tested this possibility with correspondingly patterned model “caterpillars” predated by birds in the wild. Predation rates varied with coloration and lighting in exactly the manner predicted. Such subtlety in the effects of countershading vindicates conclusions from prior evidence demonstrating stronger countershading in animals in more brightly lit habitats.
S2 from equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors SERINC5 and SERINC3
Authors: Chande Ajit , Cuccurullo Emilia Cristiana , Rosa Annachiara , Ziglio Serena , Carpenter Susan , Pizzato Massimo 
Published: November 2016

Significance
Serine incorporators (SERINC) 5 and 3 are recently discovered cellular inhibitors of retroviruses, which are incorporated into virus particles and impair their ability to propagate the infection to target cells. Only two groups of viruses (represented by HIV-1 and murine leukemia virus) had been identified as having evolved the ability to counteract SERINC inhibition. We found that equine infectious anemia virus, which causes a debilitating disease in horses, also has acquired the capacity to protect the virus particle from inhibition by SERINC5 and SERINC3 by using its small protein S2. That three different retroviruses have independently evolved the ability to elude inhibition by SERINC5 and SERINC3 indicates that these cellular factors play a fundamental role against various retrovirus pathogens.
HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia
Authors: Chakraborty Damayanti , Cui Wei , Rosario Gracy X. , Scott Regan L. , Dhakal Pramod , Renaud Stephen J. , Tachibana Makoto , Rumi M. A. Karim , Mason Clifford W. , Krieg Adam J. , Soares Michael J. 
Published: November 2016

Significance
The hemochorial placenta is a dynamic structure endowed with responsibilities controlling the extraction of maternal resources, ensuring fetal development and preserving maternal health. A healthy placenta exhibits plasticity and can adapt to environmental challenges. Such adaptations can be executed through instructive actions on trophoblast stem cells, influencing their abilities to expand and differentiate into specialized cells that accommodate the challenge. Hypoxia, when appropriately timed, promotes invasive trophoblast-directed uterine spiral artery remodeling. Hypoxia activates hypoxia inducible factor-dependent expression of lysine demethylase 3A, modifying the histone landscape on key target genes, including matrix metallopeptidase 12, which acts to facilitate trophoblast invasion and uterine vascular remodeling. Plasticity and adaptations at the maternal–fetal interface safeguard placental development and the healthy progression of pregnancy.
Selvamicin, an atypical antifungal polyene from two alternative genomic contexts
Authors: Van Arnam Ethan B. , Ruzzini Antonio C. , Sit Clarissa S. , Horn Heidi , Pinto-Tomás Adrián A. , Currie Cameron R. , Clardy Jon 
Published: November 2016

Significance
Bacteria use small molecules to mediate their relationships with nearby microbes, and these molecules represent both a promising source of therapeutic agents and a model system for the evolution and dissemination of molecular diversity. This study deals with one such molecule, selvamicin, which is produced by ant-associated bacteria. These bacteria protect the ants’ nests against fungal pathogens. Selvamicin is an atypical member of a clinically important class of antifungal agents, and it appears to have both better therapeutic properties and a different mechanism of action. Further, the genes for producing it are found on the bacteria’s chromosome in one ant nest but on a plasmid in another, illustrating the likely path by which it has spread.
Effect of electron count and chemical complexity in the Ta-Nb-Hf-Zr-Ti high-entropy alloy superconductor
Authors: von Rohr Fabian , Winiarski Michał J. , Tao Jing , Klimczuk Tomasz , Cava Robert Joseph 
Published: November 2016

Significance
High-entropy alloys are a new class of materials that consist of several principal elements arranged on simple lattices. These structures are stabilized by the high configurational entropy of the random mixing of the elements. Here, we show that the properties of a superconducting high-entropy alloy are strongly related to the electron count and that the superconducting transition temperatures of these alloys fall between those of analogous crystalline and amorphous materials. We find that despite the large degree of randomness and disorder in these alloys, the superconducting properties are nevertheless strongly dependent on the chemical composition and complexity. We argue that high-entropy alloys are excellent model systems for understanding how superconductivity and other collective quantum states evolve from crystals to amorphous solids.
Comparative Use of Shallow and Deepwater Habitats by Juvenile Pacific Salmon in the Columbia River Estuary Prior to Ocean Entry
Authors: Roegner G. Curtis , Weitkamp Laurie A. , Teel David J. 
Published: November 2016

Abstract
The degree to which fine-scale habitat use by salmonid species and stocks varies within habitat types such as estuaries is not fully resolved. We sampled shallow shoreline and deeper main-stem channel habitats in the Columbia River estuary over 3 years to compare salmon species composition, migration timing, density, size, and production type (hatchery or natural). Results indicated a high degree of spatial heterogeneity in habitat occupancy by the five salmonid species that are native to the basin. Salmonid communities at two channel habitat sites were much more similar to each other than to the community at a shoreline site. Salmonids sampled at the shoreline site were primarily subyearling Chinook Salmon Oncorhynchus tshawytscha and Chum Salmon O. keta and yearling Coho Salmon O. kisutch, with few other salmonids present. In contrast, channel habitat contained a higher diversity of salmon species, with samples representing all species of anadromous salmonids, including Sockeye Salmon O. nerka and steelhead O. mykiss. Salmonids in deeper channel habitat were generally larger than salmonids found along the shore, and the proportion of hatchery-origin salmon was also higher in deep channel habitats. On a per-area basis, we also found much higher densities of salmon along the shoreline than in channel habitats. For Chinook Salmon, habitat use also differed by genetic stock of origin: upper-river stocks primarily used deeper channels, while lower-river populations used both channel and shoreline areas. We concluded that sampling at both habitat types is required to fully encompass the migration patterns of all salmon evolutionarily significant units in the Columbia River basin. These spatial and temporal variations in salmon timing and density have ramifications for feeding, growth, and competitive interactions. This study provides information that is relevant for conservation efforts targeting specific fish populations and efforts to evaluate the potential impacts of in-water activities in the Columbia River estuary.
Received May 12, 2016; accepted August 19, 2016
Dynamics of resonant magnetic field penetration and plasma rotation
Authors: Ivanov N.V. , Kakurin A.M. 
Published: November 2016

Abstract
Results of calculations and analysis of the penetration of resonant magnetic perturbations (RMP) into tokamak plasma are presented. The TEAR code used for the calculations is based on a two-fluid magnetohydrodynamics approximation that gives coupled diffusion-type equations for the magnetic flux perturbation and for plasma rotation velocities in toroidal and poloidal directions. The radial distribution of the magnetic flux perturbation is calculated taking account of an externally applied RMP and magnetic perturbation generated by an eddy current in the resistive-vacuum vessel. The decoupling of magnetic-island velocity from the velocity of plasma rotation is employed in the calculations according to available experimental evidence and corresponding theoretical understanding. The account of this decoupling, as well as of plasma rotation in the poloidal direction in addition to the toroidal one, reduces the RMP penetration threshold and accelerates the penetration process. The main attention is paid to the dependences of the RMP penetration dynamics on the simulation conditions. The simulation findings are compared with available experimental data. Some predictions of the penetration threshold values for ITER conditions are presented.
The monotonicity and convexity for the ratios of modified Bessel functions of the second kind and applications
Authors: Yang Zhen-Hang , Zheng Shen-Zhou 
Published: November 2016

Let

K

v

(
x
)

K_{v}\left ( x\right )

be the modified Bessel functions of the second kind of order

v
v

. We prove that the function

x
↦

K

u

(
x
)

K

v

(
x
)

/

K

(
u
+
v
)

/

2

(
x
)

2

x\mapsto K_{u}\left ( x\right ) K_{v}\left ( x\right ) /K_{\left ( u+v\right ) /2}\left ( x\right ) ^{2}

is strictly decreasing on

(
0
,
∞
)

\left ( 0,\infty \right )

. Our study not only involves the Turán type inequalities, log-convexity or log-concavity of

K

v

(
x
)

K_{v}\left ( x\right )

, and the conjecture posed by Baricz, but also yields various new results concerning the monotonicity and convexity of the ratios of the modified Bessel functions of the second kind. As applications of our main theorems, some new sharp inequalities involving

K

v

(
x
)

K_{v}\left ( x\right )

are presented, which contain sharp estimates for

K

v

(
x
)

K_{v}\left ( x\right )

and sharp bounds for the ratios

K

v

′

(
x
)

/

K

v

(
x
)

K_{v}^{\prime }\left ( x\right ) /K_{v}\left ( x\right )

and

K

v
+
1

(
x
)

/

K

v

(
x
)

K_{v+1}\left ( x\right ) /K_{v}\left ( x\right )

.
Influence of Neighbor Experience and Exit on Small Farmer Market Participation
Authors: Michelson Hope C. 
Published: November 2016

AbstractThis research analyzes the motivations and dynamics of small farmer participation in supermarket supply chains in developing countries: why some small farmers join these new markets and continue their participation; why others drop out or decline the relationship from the outset. Drawing on insights from the technology‐adoption literature on learning and experimentation, and also on findings from a simple two‐period Bayesian model of farmer decisions to participate in a new market, we incorporate measures of neighboring farmers’ experience into the decision model. Results suggest that farmers delay entry to observe their neighbors’ outcomes; we find a negative relationship between the number of neighbor participants in a given period and a farmer's own decision to enter the supply chain. We find evidence that farmers delay entry for strategic reasons, allowing neighbors to bear the costs associated with a first wave of adjustment to the market, including higher product rejection rates and lower initial annual transactions with supermarkets, compared to revenues from marketing in the traditional way. Results are robust to definitions of neighbors using both administrative and geographic designations. Our results raise questions about the optimal sequence and level of farmers' market participation and exit, which remain largely unexplored in the literature.
Metabolic cost of calcification in bivalve larvae under experimental ocean acidification
Authors: Frieder Christina A. , Applebaum Scott L. , Pan T.-C. Francis , Hedgecock Dennis , Manahan Donal T. 
Published: November 2016

AbstractPhysiological increases in energy expenditure frequently occur in response to environmental stress. Although energy limitation is often invoked as a basis for decreased calcification under ocean acidification, energy-relevant measurements related to this process are scant. In this study we focus on first-shell (prodissoconch I) formation in larvae of the Pacific oyster, Crassostrea gigas. The energy cost of calcification was empirically derived to be ≤ 1.1 µJ (ng CaCO3)−1. Regardless of the saturation state of aragonite (2.77 vs. 0.77), larvae utilize the same amount of total energy to complete first-shell formation. Even though there was a 56% reduction of shell mass and an increase in dissolution at aragonite undersaturation, first-shell formation is not energy limited because sufficient endogenous reserves are available to meet metabolic demand. Further studies were undertaken on larvae from genetic crosses of pedigreed lines to test for variance in response to aragonite undersaturation. Larval families show variation in response to ocean acidification, with loss of shell size ranging from no effect to 28%. These differences show that resilience to ocean acidification may exist among genotypes. Combined studies of bioenergetics and genetics are promising approaches for understanding climate change impacts on marine organisms that undergo calcification.
Introduction
Authors: Orford Anne , Hoffmann Florian 
Published: November 2016

Abstract
This introductory chapter briefly explores the practice of theorizing international law. Theorizing is an inherent part of the practice of international law. Theories of international law have attempted to demonstrate that laws governing the conduct of sovereigns exist at all, and have been concerned with the attempt to connect emerging forms of international legal practice to a philosophical or historical tradition from which international law is said to originate, or to develop a method for interpreting or systematizing international law. The relation of international law to the modern state has been the focus of much theoretical work, both by those seeking to challenge the state’s role as the privileged subject of international law or by those seeking to argue that recognition of its importance and status have been lost.
Theorizing the Turn to History in International Law
Authors: Craven Matthew 
Published: November 2016

Abstract
This chapter focuses on the question of what was required for the productive representation of the past of international law as ‘history’ to become a meaningful activity, given the need for historical discourse and practice to be organized in temporal terms, and its past ‘found’ or ‘uncovered’. This historical consciousness fundamentally reshaped the conceptualization of what would become known as ‘international law’, and placed at centre-stage the problem of the historical method. Furthermore, not only did the emergence of this historical consciousness have specifiable theoretical and practical dimensions, it would become, as Foucault puts it, a ‘privileged and dangerous’ site, both providing theoretical sustenance to the discipline, and a space for critical engagement.
Hugo Grotius
Authors: Ittersum Martine Julia Van 
Published: November 2016

Abstract
This chapter explains how the myths surrounding Hugo Grotius (1583–1645) came into being and whose interests have been served by it. It was a combination of Dutch nationalism and the rise of modern international law that turned Grotius into a ‘founding father’, with a little help, it should be said, from the American delegates at the 1899 Hague Peace Conference. The myth is based on a highly selective reading of De Jure Belli ac Pacis and completely ignores the larger historical context of Grotius’ work, particularly his hands-on involvement in Western imperialism and colonialism. The chapter aims to contextualize properly his life and work, rather than to focus on just one aspect of it and use that to justify modern-day arrangements for the resolution of conflicts between states.
Schmitt, Schmitteanism and Contemporary International Legal Theory
Authors: Howse Robert 
Published: November 2016

Abstract
This chapter provides an overview of the concepts and arguments of Carl Schmitt (1888–1985)—Hitler’s chief legal official and an international law apologist for Nazi aggression — that have gained the most purchase in contemporary international legal discourse, primarily international legal theory. The chapter critically engages with a select group of scholars who have deployed Schmitt in contemporary international legal theory. These are: Martti Koskenniemi, Eric Posner and Adrian Vermeule, Paul Kahn, and Nehal Bhuta. Lastly, the chapter concludes with some observations about what the use of Schmitt in contemporary international legal theory may tell one about the state of the discipline, its fault lines, and anxieties.
Hannah Arendt and International Law
Authors: Whitehall Deborah 
Published: November 2016

Abstract
This chapter reconsiders the arc of Hannah Arendt’s (1906–1975) writings about international law. Her scattered remarks present a careful pattern of demands upon international law, announced at the discipline’s key formative turns, for the resolution of the Jewish Question or rather, the series of issues problematizing Jewish-ness as uncertainty about citizenship, nation, and race from the eighteenth century onward. But international law was an important site for her attention even where law was adjuvant or ancillary to the broader sweep of her analytical project. Arendt repeatedly returned to international law expecting answers as a political thinker: for the working out of tensions within the idea of nation for the sake of humankind and the plural life of politics.
The International Signs Law
Authors: Goodrich Peter 
Published: November 2016

Abstract
This chapter argues for the image as a medium for communicating the method and norms of a rather abstract, primary, and primordial jurisdiction at work during the early seventeenth-century empires. The beginnings of international law therefore are expressed in the earliest markings, patterns, rhythms, and signs that delineate human inhabitation and community. The chapter posits that the law has entered the secular world in the form of arms — symbols of rank and office — which may be used in either war or diplomacy. Another origin the chapter traces is within the realm of the sea, upon which territories and jurisdictions are often difficult to establish. Finally, international law also has its origins in legal emblems — the moveable signs, detachable images, and floating signifiers of a particular jurisdiction, which form a pan-European substrate of all legal interventions and communications.