bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting Edge: Integrin α4 Is Required for Regulatory B Cell Control of Experimental Autoimmune Encephalomyelitis
Authors: Glatigny Simon , Wagner Catriona A. , Bettelli Estelle 
Published: March 2016

Abstract
The neutralization of integrin α4 (Itga4) is currently used as treatment in multiple sclerosis. Although most studies have focused on its function on lymphocyte migration to the CNS, we have uncovered the importance of Itga4 for the generation of regulatory B cells in peripheral immune organs and their control of pathogenic T cell response and CNS pathology. Our study underscores the importance of looking at the dual role of B cells in CNS autoimmunity and provides important perspectives regarding the efficacy and side effects associated with Itga4 neutralization and other B cell–targeting therapies.
Optimal observability of the multi-dimensional wave and Schrödinger equations in quantum ergodic domains
Authors: Privat Yannick , Trélat Emmanuel , Zuazua Enrique 
Published: March 2016

We consider the wave and Schrödinger equations on a bounded open connected subset

\Omega

of a Riemannian manifold, with Dirichlet, Neumann or Robin boundary conditions whenever its boundary is nonempty. We observe the restriction of the solutions to a measurable subset

\omega

of

\Omega

during a time interval

[0, T]

with

T>0

. It is well known that, if the pair

(\omega,T)

satisfies the Geometric Control Condition (

\omega

being an open set), then an observability inequality holds guaranteeing that the total energy of solutions can be estimated in terms of the energy localized in

\omega \times (0, T)

.

We address the problem of the optimal location of the observation subset

\omega

among all possible subsets of a given measure or volume fraction. A priori this problem can be modeled in terms of maximizing the observability constant, but from the practical point of view it appears more relevant to model it in terms of maximizing an average either over random initial data or over large time. This leads us to define a new notion of observability constant, either randomized, or asymptotic in time. In both cases we come up with a spectral functional that can be viewed as a measure of eigenfunction concentration. Roughly speaking, the subset

\omega

has to be chosen so to maximize the minimal trace of the squares of all eigenfunctions. Considering the convexified formulation of the problem, we prove a no-gap result between the initial problem and its convexified version, under appropriate quantum ergodicity assumptions, and compute the optimal value. Our results reveal intimate relations between shape and domain optimization, and the theory of quantum chaos (more precisely, quantum ergodicity properties of the domain

\Omega

).

We prove that in 1D a classical optimal set exists only for exceptional values of the volume fraction, and in general one expects relaxation to occur and therefore classical optimal sets not to exist. We then provide spectral approximations and present some numerical simulations that fully confirm the theoretical results in the paper and support our conjectures.
Finally, we provide several remedies to nonexistence of an optimal domain. We prove that when the spectral criterion is modified to consider a weighted one in which the high frequency components are penalized, the problem has then a unique classical solution determined by a finite number of low frequency modes. In particular the maximizing sequence built from spectral approximations is stationary.
Accountability for Forced Displacement in Democratic Republic of Congo and Uganda before the International Criminal Court
Authors: Moffett Luke 
Published: March 2016

Accountability for Forced Displacement in Democratic Republic of Congo and Uganda before the International Criminal Court
This article examines the challenges of investigating and prosecuting forced displacement in the Central African countries of Democratic Republic of Congo and Uganda, where higher loss of life was caused by forced displacement, than by any other. In the Democratic Republic of Congo, armed groups intentionally attacked civilian populations displacing them from their homes, to cut them off from food and medical supplies. In Northern Uganda, the government engaged in a forced displacement policy as part of its counter-insurgency against the Lord’s Resistance Army, driving the civilian population into “protected villages”, where at one point the weekly death toll was over 1,000 in these camps. This article critically evaluates how criminal responsibility can be established for forced displacement and alternative approaches to accountability through reparations.
The Kenyan Cases and the Future of the International Criminal Court’s Prosecutorial Policies
Authors: Sungi Simeon P. 
Published: March 2016

The Kenyan Cases and the Future of the International Criminal Court’s Prosecutorial Policies
The Kenyan Situation pending before the International Criminal Court (ICC) is the first situation in which the prosecutor exercised his power to initiate cases “proprio motu” under Article 15 of the Rome Statute. In the wake of the comments from the former Chief Prosecutor of the International Criminal Court (ICC), Luis Moreno-Ocampo, that there was political interference from foreign diplomats during the investigation stage of the cases, it is prudent to re-examine the standards provided under the Rome Statute regarding prosecutorial discretion and evaluate the prosecutorial power and how the Kenyan cases may shape this discretionary power in order to align it with the Preamble of the Rome Statute. The Preamble affirms that the most serious crimes of concern to the international community must not go unpunished. Further, that their effective prosecution must be ensured for the purposes of ending impunity for the perpetrators of international crimes and thus to contribute to the prevention of genocide, crimes against humanity, war crimes, and crimes of aggression.
The Court Is the Political Arena: Performance and Political Narratives at the International Criminal Court
Authors: Ba Oumar 
Published: March 2016

The Court Is the Political Arena: Performance and Political Narratives at the International Criminal Court
This article explores the politics of international criminal justice and argues that the International Criminal Court is a lieu of staged performance where actors deploy their political narratives. Using the Situation in the Republic of Côte d’Ivoire before the ICC and focusing on the pre-trial phase, I contend that the defendants Laurent Gbagbo and Charles Blé Goudé project a performance and deploy political narratives that are the extension of the politics of the Ivorian crisis, which make the Court the quintessential arena where domestic and international politics cohabit with law and rules of procedure.
Addressing Impunity for Serious Crimes: The Imperative for Domesticating the Rome Statute of the ICC in Nigeria
Authors: Ibe Stanley 
Published: March 2016

Addressing Impunity for Serious Crimes: The Imperative for Domesticating the Rome Statute of the ICC in Nigeria
Over the last decade, Nigeria has witnessed several high-intensity conflicts. It became a country under preliminary investigation by the International Criminal Court (ICC) following allegations of serious crimes. In 2013, the boko haram insurgency was classified as a “non-international armed conflict.” Commentators appear divided over the capacity and willingness of domestic institutions to manage crimes arising from or connected with conflicts in Nigeria. Those who argue for unwillingness often point to the struggle to domesticate the Rome Statute of the International Criminal Court (Rome Statute) as one of the clearest indication that there is not sufficient interest. This article interrogates the question of seeming impunity for serious crimes in Nigeria and makes a case for domesticating the Rome Statute through an amendment to the Crimes against Humanity, War Crimes, Genocide and Related Offences Bill, 2012 pending before the National Assembly.
Two types of volcanic tremor changed with eruption style during 1986 Izu‐Oshima eruption
Authors: Kurokawa Aika , Takeo Minoru , Kurita Kei 
Published: March 2016

AbstractVolcanic tremor provides clues to magma migration pathways so that tremor source location is expected to be an efficient tool for tracking dynamic behavior of magma in evolution of eruptive activity. However, clear evidence, which connects between temporal variation in volcanic tremor and evolution of eruption style, is still lacking. We have analyzed volcanic tremors occurred during 1986 Izu‐Oshima eruption using recently digitized data. The results present a clear link between eruption styles, waveform variations and source locations of the tremors. Moreover, precursory activity of the tremors that indicates injection of magma below fissures has been clarified 5 days prior to the fissure eruptions. This demonstrates predominance of tremor activity as an adaptive monitoring tool in volcanic eruption.
Injection‐induced seismicity on basement faults including poroelastic stressing
Authors: Chang K. W. , Segall P. 
Published: March 2016

AbstractMost significant induced earthquakes occur on faults within the basement beneath sedimentary cover. In this two‐dimensional plane strain numerical study, we examine the full poroelastic response of basement faults to fluid injection into overlying strata, considering both (1) the permeability of the fault zone and (2) the hydraulic connectivity of the faults to the target horizon. Given hydraulic and mechanical properties, we compute the spatiotemporal change in Coulomb stress, which we separate into (1) the change in poroelastic stresses Δτs+fΔσn, where Δτs and Δσn are changes in shear and normal stress (Δτs>0 and Δσn>0 both favor slip), and (2) the change in pore pressure fΔp. Pore pressure diffusion into hydraulically connected, permeable faults dominates their mechanical stability. For hydraulically isolated or low‐permeability faults, however, poroelastic stresses transmitted to deeper basement levels can trigger slip, even without elevated pore pressure. The seismicity rate on basement fault zones is predicted using the model of Dieterich (1994). High seismicity rates can occur on permeable, hydraulically connected faults due to direct pore pressure diffusion. Lower rates are predicted on isolated steeply dipping normal faults, caused solely by poroelastic stressing. In contrast, seismicity on similarly oriented reverse faults is inhibited.
Gravity Models and Asymmetric Exchange Rate Effects: Insights from German Beer Exports
Authors: Dreyer Heiko , Fedoseeva Svetlana 
Published: March 2016

ABSTRACTRecent developments in trade literature suggest that in the presence of strategic pricing in some markets and an incomplete exchange rate pass‐through resulting from it, the standard gravity model has to be augmented with an exchange rate variable. As symmetry of pass‐through has been questioned in new pricing‐to‐market (PTM) studies, we argue that this asymmetric impact of the exchange rate on trade should be explicitly modeled within the gravity framework. This consideration of asymmetric effects of exchange rate appreciations and depreciations on export values and quantities might provide insights into the driving forces of PTM in a particular market (or group of markets) given that the existing literature emphasizes two main hypotheses that explain the occurrence of an asymmetric PTM (market share hypothesis and marketing bottleneck hypothesis). In this paper, we propose a way to integrate individual (asymmetric) long‐run effects of currency appreciations and depreciations on trade flows into the gravity model and empirically investigate which of the driving forces is relevant for the case of German beer exports. PTM studies often argue that the market share protection is a reason for local currency price stabilization mechanisms applied in the most important markets. Yet, the results of our analysis reveal that this might no longer be the case when all trading partners are considered. [EconLit citations: C33; F14; L66].
N‐Heterocyclic carbenes derived from imidazo‐[1,5‐a]pyridines related to natural products: synthesis, structure and potential biological activity of some corresponding gold(I) and silver(I) complexes
Authors: Mihorianu Monica , Franz M Heiko , Jones Peter G , Freytag Matthias , Kelter Gerhard , Fiebig Heinz‐Herbert , Tamm Matthias , Neda Ion 
Published: March 2016

A series of Au(I) complexes (12, 13, 14, 15, 16) and Ag(I) complexes (17, 18, 19, 20) derived from imidazo[1,5‐a]pyridin‐3‐ylidenes were synthesized from AuCl(SMe2) or by reacting silver(I) acetate with 2,5‐dimethylimidazo[1,5‐a]pyridin‐2‐ium iodide or imidazo[1,5‐a]pyridin‐2‐ium salts, and were characterized using NMR spectroscopy, mass spectrometry and elemental analyses. In addition, the Au(I) complex 13 and the Ag(I) complex 19 were characterized using single‐crystal X‐ray diffraction. Using paclitaxel as a standard, all Au(I) and Ag(I) N‐heterocyclic carbene complexes were evaluated for their in vitro anti‐tumour activity against 12 cell lines using a monolayer cell survival and proliferation assay. The highest anticancer activity was found for complexes 15, 13 and 14 with mean IC50 values of 10.09, 10.42 and 12.28 μM, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
Development and characterization of an in vitro model of colorectal adenocarcinoma with MDR phenotype
Authors: Cinci Lorenzo , Luceri Cristina , Bigagli Elisabetta , Carboni Ilaria , Paccosi Sara , Parenti Astrid , Guasti Daniele , Coronnello Marcella 
Published: March 2016

AbstractThe major cause of failure in cancer chemotherapy is the development of multidrug resistance (MDR), and the characterization of biological factors involved in this response to therapy is particularly needed. A doxorubicin‐resistant HCT‐8/R clone was selected from sensitive parental cells and characterized analyzing several parameters (cell cycle phase distribution, apoptotic activity, expression, distribution and functionality of the P‐gp efflux pump, the response to other chemotherapy agents, its ultrastructural features, invasiveness, and transcriptomic profile). HCT‐8/R cells showed a peculiar S phase distribution, characterized by a single pulse of proliferation, resistance to drug‐mediated apoptosis, increased expression and functionality of P‐gp and overexpression of stem cell markers (CD44 and aldehyde dehydrogenase 1A2). At the ultrastructural level, HCT‐8/R presented a greater cell volume and several intracytoplasmic vesicles respect to HCT‐8. Moreover, the resistant clone was characterized by cross resistance to other cytotoxic drugs and a greater capacity for migration and invasion, compared to parental cells. Our data reinforce the concept that the MDR phenotype in HCT‐8/R cells is multifactorial and involves multiple mechanisms, representing an interesting tool to understand the biological basis of MDR and to test strategies that overcome resistance to chemotherapy.
Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia
Authors: Spencer Nick J. , Kyloh Melinda , Beckett Elizabeth A , Brookes Simon , Hibberd Tim 
Published: March 2016

ABSTRACTIn visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran‐amine were made into thoracic DRGs (T8–T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene‐related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple‐type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064–3083, 2016. © 2016 Wiley Periodicals, Inc.
Evolution of the northern Tethyan Helvetic Platform during the late Berriasian and early Valanginian
Authors: Morales Chloe , Spangenberg Jorge E. , Arnaud‐Vanneau Annie , Adatte Thierry , Föllmi Karl B. 
Published: March 2016

AbstractThe Early Cretaceous period is characterized by widespread carbonate production in tropical and subtropical epicontinental seas, which was modulated by changes in sea‐level, detrital and nutrient fluxes, and the global carbon cycle. As a result, carbonate platforms were sensitive recorders of environmental change, which often anticipated global environmental perturbations. A good example is provided by the northern Tethyan carbonate platform, which is presently preserved in the central European Helvetic Alps. There, the latest early to late Valanginian Weissert episode of global change, which is defined by the first important positive shift in δ13C records of the Cretaceous, is expressed by a prolonged, stepwise drowning phase. In this contribution, a detailed reconstruction of palaeoenvironmental change before and during the Weissert episode is provided based on three representative sections of the Helvetic platform. The sections are placed along a deepening transect and correlated by means of ammonite and microfossil biostratigraphy, sequence stratigraphy and δ13C chemostratigraphy. In a first phase of palaeoenvironmental change during the latest Berriasian, photozoan carbonate production was stopped by a major and hitherto undetected drowning episode, which was followed by a phase of renewed carbonate production by heterozoan biota. This phase was linked to major sea‐level rise, a change to a more humid climate and strong regional subsidence associated with tectonic block tilting. During the Valanginian, the circulation of nutrient‐enriched sea waters prevented a return to oligotrophic conditions and two further drowning episodes occurred, which are both documented by condensed phosphate‐rich beds and dated as middle early Valanginian and late Valanginian to early Hauterivian. The exact causes of the three‐step deterioration in carbonate production are not established but a link to episodic volcanic activity is likely, eventually related to the formation of the Paranà‐Etendeka large igneous province.
Bitter taste perception and TAS2R38 genotype: effects on taste sensitivity, food consumption and anthropometry in Mexican adults
Authors: Barajas‐Ramírez Jahir A. , Quintana‐Castro Rodolfo , Oliart‐Ros Rosa M. , Angulo-Guerrero Ofelia 
Published: March 2016

AbstractDifferences in sensitivity to 6‐n‐propylthiouracil (PROP) are associated with TAS2R38 genotypes. Those differences allow the classification in “nontasters” (NT), “tasters” (MT) and “supertasters” (ST), which have been related to differences in taste acuity and nutritional status, although there is controversy in the results obtained by different research groups. The aim of this study was to determine the frequencies of NT, MT and ST, TAS2R38 genotypes and to analyze its relationship with taste sensitivity, food consumption and anthropometric measures in healthy Mexican adults. Body Mass Index (BMI), Waist Circumference (WC), TAS2R38 genotype, detection thresholds for sucrose, capsaicin, PROP and linoleic acid as well as intensity perceived for sucrose, capsaicin and PROP suprathreshold solutions were performed in 76 Mexican adults. Food restriction was assessed and two seven‐day food consumption records from 66 individuals were analyzed. The proportion of subjects with genotype AVI/AVI, and its associated phenotype NT, was close to 10%; the proportion of MT and ST was 54.6 and 31.8 respectively. Genotypes associated with ST were present in 38%, while those associated with MT accounted for 41% of the population. PROP sensitivity was associated with linoleic acid sensitivity, consumption of vegetables, grains and dairy foods. BMI and WC were negatively correlated to carbohydrate intake and linoleic acid detection threshold. PROP taster status and TAS2R38 genotypes were related. PROP and linoleic acid sensitivity influences food consumption in unrestrained eaters and could produce differences in long‐term nutritional status. Copyright © 2016 John Wiley & Sons, Ltd.
Patterns and persistence of behavioural and psychological symptoms in those with cognitive impairment: the importance of apathy
Authors: van der Linde Rianne M , Matthews Fiona E , Dening Tom , Brayne Carol 
Published: March 2016

ObjectiveTo study the stability and emergence of a range of behavioural and psychological symptoms (BPS), their association with mortality and the effect of covariates on these transitions in a population‐based study of cognitively impaired older people with a long follow‐up period and large sample size, with a particular focus on apathy.MethodsData were from a population‐based, longitudinal cohort study of ageing. Interviews were conducted at 0, 2, 6, 8 and 10 years with 3626 participants aged 65+. The persistence of 11 BPS and their association with mortality in those with cognitive impairment (MMSE 25 or below) was investigated using multi‐state models, allowing us to take into account estimations of the probability of transitions that occurred in the time between interviews.ResultsMost BPS were persistent. Apathy was one of the most stable symptoms; in those with apathy, the probability of still having apathy after 1 year is 62%. Apathy, sleep problems, depression, irritability and wandering were most likely to develop. BPS are associated with mortality; in those with apathy, mortality is 3.1 times more likely than in those without apathy. Low cognitive function and dementia were associated with emergence of new symptoms.ConclusionsThis population‐based, multi‐centre study with a follow‐up period of 10 years showed that BPS are associated with mortality and most symptoms are persistent. Apathy was characterised by a high prevalence, a high persistence and a strong association with mortality, and has a negative impact on disability, management of other disease and caregiver burden.