bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutional Pluralism Revisited
Authors: Walker Neil 
Published: June 2016

AbstractThis essay revisits the theory of constitutional pluralism. This theory was first developed in the EU context as a way of understanding and defending the absence of a broadly agreed source of final authority in the relationship between national and supranational (EU) legal systems and their respective appellate courts in the context of the significant increase in supranational jurisdiction around the time of the Maastricht Treaty 25 years ago. The essay argues that the theory of constitutional pluralism remains relevant today, in particular offering better explanatory and justificatory accounts of the EU than any of the singularist (or monist), holist or federalist alternatives. Its continuing relevance, however, depends on a more explicit focus on the political underpinnings of the legal and judicial dimensions of constitutional pluralism than has typically been the case in the literature, and on more detailed consideration of the preconditions, forms and limits of constitutional initiative in the contemporary phase of unprecedented challenge to the legitimacy of the EU.
Another Look at Constitutional Pluralism in the European Union
Authors: Baquero Cruz Julio 
Published: June 2016

AbstractConstitutional pluralism is a theory, or movement, or idea, for some perhaps even an ideal, about the relationship between the legal system of the European Union and those of its Member States. In this paper, Julio Baquero Cruz analyses its assumptions and implications in the light of historical experience and of the consequences it could have for the practice of law in Europe. To do so, constitutional pluralism is compared with the other main positions about that relationship: the national constitutional position and the position of Union law.
Politicising EU Lawmaking? The Spitzenkandidaten Experiment as a Cautionary Tale
Authors: Goldoni Marco 
Published: June 2016

AbstractThe Spitzenkandidaten experiment has elicited much interest in academic and political circles as a move towards further politicisation of important aspects of EU lawmaking. This article puts forward a sobering account of the normative and instrumental reasons that explain why these expectations were grounded on shaky premises and the experiment could not have delivered its promises. In particular, the article stresses (1) the failure in creating a channel for political opposition through the indirect election of the President of the Commission; (2) the adoption of a formal understanding of the institutions involved in the process, that is, a conception detached from their social basis and (3) the choice of the wrong institution for the purpose of politicisation. The article concludes with a modest proposal for the consolidation of the channels for political action already available at the level of the Member States.
A new conception for enhancement of fatigue life of large number of fastener holes in aircraft structures
Authors: Duncheva G. V. , Maximov J. T. , Ganev N. 
Published: June 2016

AbstractA new conception for increasing fatigue life of large number of fastener holes in aircraft structures is developed. It is accomplished by a new method, called friction stir hole expansion (FSHE). This method not only reduces labour and time consumption, but it also decreases the overall cost for processing a large number of holes in structures made of aerospace grade 2024‐T3 aluminium alloy. FSHE combines the advantages of friction stir processing with these of mandrel cold working methods in two ways: a micro effect, expressed in hole surface modification, and a macro effect, expressed by the introduction of beneficial compressive residual macro stresses. The effectiveness of the method has been assessed by fatigue tests. Finite element simulations have been carried out. It has been proven that the greater fatigue life of fastener holes, processed by FSHE, is a consequence of the obtained micro effect.
Stoichiometric constraints modulate impacts of silver contamination on stream detritivores: an experimental test with Gammarus fossarum
Authors: Arce‐Funck Julio , Crenier Clément , Danger Michael , Cossu‐Leguille Carole , Guérold François , Felten Vincent 
Published: June 2016

Summary

Organisms commonly face multiple stresses in ecosystems, among which are toxic substances that add to natural ecological constraints such as insufficient resource quality. The combined effects of these stressors on species and ecosystems remain poorly investigated.

We hypothesised that feeding on high‐quality resources in terms of phosphorus (P) content will improve the physiological state of consumers and thus increase tolerance to episodic metal stress by silver (Ag). We used a detritivorous crustacean from streams, Gammarus fossarum, to test this hypothesis.

The experimental design involved two phases. In the first phase, gammarids were fed ad libitum for 15 days to evaluate the effect of food quality on their energetic status. Gammarids were placed in laboratory microcosms and allowed to feed on two leaf species, alder and sycamore, that were colonised by aquatic fungi and experimentally enriched with P. At the end of this feeding period, we determined (i) food consumption, (ii) energetic reserves and (iii) physiological and behavioural states. In the second phase, gammarids previously consuming food of different quality were exposed to dissolved Ag (0, 0.5 and 1 μg L−1) for 4 days to investigate the physiological and behavioural responses of the consumers.

Elevated P concentrations in leaf litter increased the energetic reserves and locomotor activity of G. fossarum. Gammarids exposed to Ag had a low glycogen content, regardless of the Ag concentration and leaf P concentration, suggesting significant energy allocation to several aspects of organism maintenance (e.g. detoxification or compensatory mechanisms). In most cases, this investment appeared to prevent gammarids from carrying out lipid peroxidation (indicating cell membrane damage), except for those gammarids feeding on leaves with the highest P concentration.

Higher energetic storage (measured as glycogen content), related to higher elemental food quality, did not lead to a systematic increase in consumer tolerance to Ag, gammarids being unable to compensate for negative effects of Ag at the concentrations tested.
Clinical and virological features of acute hepatitis E in Gunma prefecture, Japan between 2004 and 2015
Authors: Yamazaki Yuichi , Naganuma Atsushi , Arai Yosuke , Takeuchi Suguru , Kobayashi Takeshi , Takakusagi Satoshi , Hatanaka Takeshi , Hoshino Takashi , Namikawa Masashi , Hashizume Hiroaki , Takizawa Daichi , Ohyama Tatsuya , Suzuki Hideyuki , Horiguchi Norio , Takagi Hitoshi , Sato Ken , Kakizaki Satoru , Kusano Motoyasu , Nagashima Shigeo , Takahashi Masaharu , Okamoto Hiroaki , Yamada Masanobu 
Published: June 2016

AimTo evaluate the clinical and virological features of acute hepatitis E (AH‐E) in Gunma prefecture and focus on the hepatitis E virus (HEV) infection in immunocompromised patients.MethodsA total of 30 patients with AH‐E diagnosed at our Gunma University Hospital, and located in 3‐39‐15 Showa‐machi, Maebashi, Gunma 371‐8511 Japan, and its affiliated hospitals from 2004 to 2015, were studied. We evaluated the detailed medical histories, laboratory examinations and virological features of these participants.ResultsOf the 30 patients, 21 patients were men, with a median age of 61 years. Three of these patients had a history of recent oversea travel. A total of 14 patients had eaten raw or undercooked meat/viscera from animals, and two patients had contracted transfusion‐transmitted AH‐E. Eight patients were immunocompromised, including those with hematological disease, cancer receiving systemic chemotherapy and kidney transplant or connective tissue disease undergoing immunosuppressive medications. The alanine aminotransferase and total bilirubin levels were more significantly reduced in these immunocompromised patients than in the non‐immunocompromised patients. Severe thrombocytopenia, an extra‐hepatic manifestation of AH‐E, occurred in one case. Among the 22 HEV strains whose subgenotype was determined, two were imported strains (1a and 1f), and 11 strains formed four distinct phylogenetic clusters within subgenotype 3b. The remaining nine strains differed from each other by 9.8–22.4%, and were classified into four subgenotypes (3a, 3b, 3e and 3f).ConclusionMarkedly divergent HEV strains (3a, 3b, 3e and 3f) were found to circulate in Gunma. Although immunosuppression appears to play a crucial role in establishing chronic sequels, AH‐E in eight immunocompromised patients, including transfusion‐transmitted HEV infection in two patients, did not become chronic.
Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers
Authors: Yin Liqun , Xu Jie , Li Min , Reddy Vishnu , Zhou Quan , Liu Huanxin , Chu Peiguo , Zhang Qianyun , Huang Qin , Gao Zifen , Liang Xiayuan , Wang Huan‐You , Pan Zenggang 
Published: June 2016

AimsRare cases of B cell lymphomas do not express conventional B cell markers (CD20, CD79a and PAX5), and these types of lymphomas include anaplastic lymphoma kinase (ALK)‐positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma and the solid variant of primary effusion lymphoma, extracavitary human herpesvirus 8 (HHV8)‐positive large B cell lymphoma. Establishing accurate diagnoses of these B cell lymphomas can be challenging, and often requires a large panel of immunohistochemical stains, molecular assays and cytogenetic studies. B cell‐specific transcription factors, Oct2 and Bob1, have been shown to be expressed consistently in most, if not all, B cell lymphomas, and therefore we investigated the utility of Oct2 and Bob1 immunohistochemistry in lineage determination of the aforementioned B cell lymphomas.Methods and resultsWe selected 34 cases of previously diagnosed B cell lymphomas with no or weak expression of CD20, CD79a and PAX5. Oct2 and Bob1 were positive in 74% (25 of 34) and 85% (29 of 34) of the cases, respectively. When we combined the results of these two immunostains, 94% (32 of 34) cases expressed at least one of these two markers. We also included 51 control cases of non‐B cell neoplasms, and none of them expressed either Oct2 or Bob1.ConclusionsOct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan‐B cell markers, and it should provide great diagnostic benefit to include them both in a panel of immunohistochemistry to assess undifferentiated malignant neoplasms.
Molecular diagnosis of thrombocytopenia‐absent radius syndrome using next‐generation sequencing
Authors: Nicchia E. , Giordano P. , Greco C. , De Rocco D. , Savoia A. 
Published: June 2016

SummaryIntroductionThrombocytopenia‐absent radius (TAR) syndrome is a rare autosomal recessive disease. Patients are compound heterozygotes for a loss‐of‐function allele, which in most cases is a large genomic deletion on chromosome 1q21.1 containing the RBM8A gene, and a noncoding variant located in the 5′UTR (rs139428292) or intronic (rs201779890) regions of RBM8A. As the molecular genetic testing in TAR requires multiple techniques for detection of copy‐number variations (CNV) and nucleotide substitutions, we tested whether a next‐generation sequencing (NGS) approach could identify both alterations.MethodsTwo unrelated families were analyzed with Ion PGM sequencing using a target panel of genes responsible for different forms of inherited thrombocytopenia. A statistical quantitative evaluation of amplicon coverage was performed to detect CNV, in particular those on the RBM8A gene.ResultsAll the probands were apparently homozygous for the rare allele inherited by the father at the rs139428292 locus, suggesting the presence of a deletion on the maternal chromosome. The statistical analysis confirmed the hemizygous condition of RBM8A.ConclusionWe concluded that NGS approaches could be used as a cost‐effective method for molecular investigation of TAR as they could simultaneously detect CNV and point mutations.
Performance evaluation of the Sysmex®XP‐300 in an oncology setting: evaluation and comparison of hematological parameters with the Sysmex®XN‐3000
Authors: van Dievoet M. A. , Louagie H. , Ghys T. 
Published: June 2016

SummaryIntroductionThe Sysmex XP‐300® (XP‐300) is a new, fully automated hematology analyzer, designed to generate complete blood counts (CBC) with 3‐part differential. In our study, the XP‐300 was evaluated as a point‐of‐care (POC) analyzer in an oncology setting. In which blood samples from patients with different pathologies and treatments, affecting hematopoiesis, were analyzed.MethodsPerformance was evaluated according to the International Council for Standardization in Haematology (ICSH) guidelines and CLSI protocol H20‐A2 . Beside precision, linearity and carry‐over, a comparison study with the Sysmex® XN‐3000 (XN‐3000) and a manual reference leukocyte differential was performed. Flagging performance was also evaluated.ResultsXP‐300 showed excellent precision and linearity results. For within‐ and between‐run precision, the criteria, according to Ricos et al. , were met for all parameters tested, except for platelets in the low level. Less than or equal to 0.5% carry‐over was seen for all parameters tested. Comparison studies showed an acceptable correlation with both XN‐3000 and the manual reference leukocyte count. A suboptimal flagging performance was demonstrated.ConclusionIn the context of diagnosing cytopenia due to myelosuppressing agents or leukocytosis due to infection, the XP‐300 showed good analytical performance. However, in the thrombocytopenic range, precision was suboptimal. In follow‐up of hematological malignancies with the occurrence of abnormal cells, we advise verification with a more advanced analyzer or with microscopic review, although further studies with a higher prevalence of abnormal cells are needed.
Evaluation of a new PT‐INR monitoring system in patients with the antiphospholipid syndrome
Authors: Braham S. , Novembrino C. , Moia M. , Torresani E. , Tripodi A. 
Published: June 2016

SummaryIntroductionPatients on anticoagulant therapy with vitamin K antagonists (VKA) need frequent INR monitoring. Reliability of point‐of‐care (POC) devices for measuring INR needs rigorous evaluation, particularly in patient with the antiphospholipid syndrome (APS). The aim of this study was to evaluate the accuracy of the ProTime InRhythm™ System (here called device) for INR measurement in patients with APS on VKA.MethodsWe compared the device INR vs. the laboratory INR measurement for blood samples from 29 APS‐positive and 31 APS‐negative patients consecutively enrolled. APS was confirmed by positive serological and/or phospholipid‐dependent coagulation tests. Chromogenic factor X assay was used to evaluate anticoagulation. Bland–Altman difference plot for paired INR (POC vs. laboratory) was used to evaluate agreement between the device and the laboratory. The device INR relationship with factor X chromogenic assay was evaluated by orthogonal regression analysis.ResultsOverall, 97% of the device INR measurements were similar to laboratory INR values with an absolute difference less than 0.4 units. Correlation coefficient for the device INR vs. factor X was −0.69 (P < 0.0001, CI 95% −0.80 to −0.52).ConclusionsThe ProTime InRhythm System™ is an accurate point‐of‐care device for measuring INR also in patients with and without APS.
Queen pheromone regulates programmed cell death in the honey bee worker ovary
Authors: Ronai I. , Oldroyd B. P. , Vergoz V. 
Published: June 2016

AbstractIn social insect colonies the presence of a queen, secreting her pheromones, is a key environmental cue for regulating the reproductive state of workers. However, until recently the proximate molecular mechanisms underlying facultative worker sterility were unidentified. Studies into worker oogenesis in the honey bee (Apis mellifera) have indicated that programmed cell death is central to the regulation of oogenesis. Here we investigate how queen pheromone, age of the worker and ovary state affect both programmed cell death and cell number in worker ovaries. We describe a novel method to simultaneously measure programmed cell death (caspase activity) and live cell number (estimated from the amount of adenosine triphosphate) in an insect tissue. Workers exposed to queen pheromone have higher levels of caspase activity in the ovary than those not exposed. Our results suggest that queen pheromone triggers programmed cell death at the mid‐oogenesis checkpoint causing the abortion of worker oocytes and reproductive inhibition of the worker caste. Nonetheless, high caspase activity is present in activated ovaries from workers not exposed to queen pheromone. This caspase activity is most likely to be from the nurse cells undergoing programmed cell death, in late oogenesis, for normal oocyte development. Our study shows that the social environment of an organism can influence programmed cell death within a tissue.
Emerging roles for antigen presentation in establishing host–microbiome symbiosis
Authors: Bessman Nicholas J. , Sonnenberg Gregory F. 
Published: June 2016

SummaryTrillions of beneficial bacteria inhabit the intestinal tract of healthy mammals from birth. Accordingly, mammalian hosts have evolved a series of complementary and redundant pathways to limit pathologic immune responses against these bacteria, while simultaneously protecting against enteric pathogen invasion. These pathways can be generically responsive to the presence of any commensal bacteria and innate in nature, as for IL‐22‐related pathways. Alternatively, specific bacterial antigens can drive a distinct set of adaptive immune cell responses, including IgA affinity maturation and secretion, and a recently described pathway of intestinal selection whereby MHCII+ ILC3 deletes commensal bacteria‐reactive CD4 T cells. These pathways can either promote or inhibit colonization by specific subsets of commensal bacteria, and cooperatively maintain intestinal homeostasis. In this review, we will highlight recent developments in understanding how these diverse pathways complement each other to cooperatively shape the symbiotic relationship between commensal bacteria and mammalian hosts.
The processing and presentation of lipids and glycolipids to the immune system
Authors: Vartabedian Vincent F. , Savage Paul B. , Teyton Luc 
Published: June 2016

SummaryThe recognition of CD1–lipid complexes by T cells was discovered 20 years ago and has since been an emerging and expanding field of investigation. Unlike protein antigens, which are presented on MHC class I and II molecules, lipids can only be presented by CD1 molecules, a unique family of MHC‐like proteins whose singularity is a hydrophobic antigen‐binding groove. The processing and loading of lipid antigens inside this groove of CD1 molecules require localization to endosomal and lysosomal subcellular compartments and their acidic pHs. This particular environment provides the necessary glycolytic enzymes and lipases that process lipid and glycolipid antigens, as well as a set of lipid transfer proteins that load the final version of the antigen inside the groove of CD1. The overall sequence of events needed for efficient presentation of lipid antigens is now understood and presented in this review. However, a large number of important details have been elusive. This elusiveness is linked to the inherent technical difficulties of studying lipids and the lipid–protein interface in vitro and in vivo. Here, we will expose some of those limitations and describe new approaches to address them during the characterization of lipids and glycolipids antigen presentation.
Antigen‐specific impairment of adoptive T‐cell therapy against cancer: players, mechanisms, solutions and a hypothesis
Authors: Villadangos Jose A. 
Published: June 2016

SummaryAdoptive cell therapy (ACT) destroys tumors with infused cytotoxic T lymphocytes (CTLs). Although successful in some settings, ACT is compromised due to impaired survival or functional inactivation of the CTL. To better understand the mechanisms involved, we have exploited a mouse model of leukemia expressing ovalbumin as a tumor neoantigen to address these questions: (i) Is CTL impairment during ACT antigen specific? (ii) If yes, which are the antigen‐presenting cells responsible? (iii) Can this information assist the development of complementary therapies to improve ACT? Our results indicate that the target (tumor) cells, not cross‐presenting cells, are the main culprits of antigen‐specific CTL inactivation. We find that the affinity/avidity of the CTL‐tumor cell interaction has little influence on ACT outcomes, while tumor density is a major determinant. Reduction of tumor burden with mild non‐lymphoablative and non‐inflammatory chemotherapy can dramatically improve the efficacy of ACT and may minimize side‐effects. We propose a general mechanism for the inactivation of anti‐self CTL in the same tissues where the activity of anti‐foreign CTL is preserved, based on the density of target cells. This mechanism, which we tentatively call stunning, may have evolved to protect infected sites from self‐destruction and is exploited by tumors to inactivate CTL.
Nowhere to hide: unconventional translation yields cryptic peptides for immune surveillance
Authors: Starck Shelley R. , Shastri Nilabh 
Published: June 2016

SummaryEffective immune surveillance by CD8+ cytotoxic T cells of intracellular microbes and cancer depends on the antigen presentation pathway. This pathway produces an optimal peptide repertoire for presentation by major histocompatibility (MHC) class I molecules (pMHCs I) on the cell surface. We have known for years that the pMHC I repertoire is a reflection of the intracellular protein pool. However, many studies have revealed that pMHCs I present peptides not only from precursors encoded in open‐reading frames of mRNA transcripts but also cryptic peptides encoded in apparently ‘untranslated’ regions. These sources vastly increase the availability of peptides for presentation and immune evasion. Here, we review studies on the composition of the cryptic pMHC I repertoire, the immunological significance of these pMHC I, and the novel translational mechanisms that generate cryptic peptides from unusual sources.