bluuebunny/crossref_metadata_2025 huggingface dataset:
The International Responsibility of the European Union—The EU Perspective: Between Pragmatism and Proceduralisation
Authors: Casteleiro Andrés Delgado
Published: January 2014

EU management of its international responsibility for wrongful acts varies between a pragmatic approach and the proceduralisation of its responsibility. The EU either lays down complex procedures in order to manage the allocation of responsibility in order to (allegedly) preserve the internal division of competences or takes a pragmatic approach which disregards any internal division of competences. This chapter critically analyses these two trends in EU practice. More precisely, it identifies from the ongoing development in the incipient foreign direct investment policy of the EU and in its accession to the European Convention on Human Rights the problems linked to this way of managing the EU’s international responsibility. Overall, it argues that instead of complex and slow procedures or ad hoc pragmatic solutions, the EU should adhere to a rule-based approach which is at the same time pragmatic and respects the principles underpinning the proceduralisation of responsibility.
Beyond the Control Paradigm? International Responsibility and the European Union
Authors: Hernández Gleider I
Published: January 2014

From the perspective of public international law, the legal personality of the European Union (EU) carries with it the possibility for it to exercise rights and to bear obligations on the international plane. Its quasi-federal structure, however, requires consideration as to how these rights and obligations may be exercised. In this chapter, two regimes are compared: the EU’s rights and obligations as an international organisation and the possibility that its internal structures might be recognised on the international plane, thus leading to more complex notions of subsidiary responsibility, shared between the various levels of European governance.
The Area of Freedom, Security and Justice in the Light of the EU Accession to the ECHR—Is the Break-up Inevitable?
Authors: Kornezov Alexander
Published: January 2014

Even though the decision to accede to the European Convention on Human Rights and Fundamental Freedoms (ECHR) is a fait accompli, the terms under which the accession should take place are still very much open to debate. The present chapter focuses specifically on the possible tensions which may arise in the aftermath of the EU’s accession to the ECHR in four of the core elements of the EU area of freedom, security and justice (AFSJ): recognition and enforcement of judgments in civil and commercial matters, wrongful removal or retention of a child, the Common European Asylum System and the European Arrest Warrant. It then puts forward a number of solutions which could be included either in the accession agreement itself or in the post-accession case law of the ECtHR and which allow not only for the preservation of the coherence and integrity of the AFSJ but also for external judicial control on human rights matters in the AFSJ.
From ‘Don’t Mention theTitanium DioxideJudgment’ to ‘I Mentioned it Once, But I Think I Got Away with it All Right’: Reflections on the Choice of Legal Basis in EU External Relations after theLegal Basis for Restrictive MeasuresJudgment
Authors: de Baere Geert
Published: January 2014

This chapter examines the choice of legal basis in EU external relations post-Lisbon in the light of the judgment of the Court of Justice in theLegal Basis for Restrictive Measurescase. Before reaching the conclusion that the regulation at issue there was rightly based on Article 215(2) of the Treaty on the Functioning of the European Union (TFEU) and rejecting the European Parliament’s argument that the measure ought to have been taken on the basis of Article 75 TFEU, the Court made a number of important observations on the principles to be followed when choosing a legal basis and recalled some of its earlier case law, in particularTitanium Dioxideand its progeny. This chapter reflects upon the application of those principles in a post-Lisbon framework.
Ready to Do Whatever it Takes? The Legal Mandate of the European Central Bank and the Economic Crisis
Authors: Wilsher Daniel
Published: January 2014

To complement the ‘no shared liability’ rule and public deficit limits, the Maastricht Treaty gave the European Central Bank (ECB) a narrow remit to focus on price stability. Crucially, as a ‘non-sovereign’ central bank, it was unclear that the ECB would act as lender of last resort in the event of market panics. The neoliberal orthodoxy at the heart of Economic and Monetary Union (EMU) held that moral hazard and inflationary risks militated against anything resembling ‘illegal monetary financing’. Following monetary union, markets under-priced risks and encouraged bubbles, but, with the onset of the crisis, sentiment overshot the other way, starving credit from banks and later sovereigns. With bailout funds limited and austerity failing to improve debt spreads, sovereigns became illiquid. ECB officials reluctantly concluded that an uncontrolled sovereign default would threaten the continuation of monetary union. The ECB was thus forced de facto to expand its mandate, first to help banks and, later, to help sovereigns facing loss of access to bond markets. Ultimately this was successful in restoring confidence, but the ECB remained uncomfortable with its role. It has continued to stress its legal limitations and has pressed for reformed governance to enforce fiscal discipline. The economic case for a lender of last resort in a crisis was always strong, but brings with it a worsening moral hazard problem that may invite leaders to avoid the deeper political changes necessary to rebalance the Eurozone.
EU Development Policy: Constitutional and Legislative Foundation(s)
Authors: Schütze Robert
Published: January 2014

The Union’s constitutional regime for development policy has traditionally progressed alongside two parallel tracks. In addition to a general regime for all developing countries, there exists a special regime for African, Caribbean and Pacific Countries (ACP countries). The Union’s general development policy originated as a flanking policy within the Common Commercial Policy. This trade-centricity was only relativised by the insertion of an express development aid competence in 1992. The Union’s development cooperation competence can today be found in Article 209 of the Treaty on the Functioning of the European Union (TFEU) and allows the Union to adopt legislative acts or conclude international agreements to reduce poverty within developing countries. By contrast, the Union’s special development regime has had a very different constitutional source. It stemmed from the ‘colonial’ association to the Union (quaits Member States) of certain dependent ‘oversees countries and territories’ for which the 1957 Treaty of Rome had provided a limited development competence. Once these countries gained independence in the 1960s, however, the Union had to transfer this special regime to its contractual association competence under Article 217 TFEU. The association regime for ACP countries has itself undergone a number of significant changes with the transition from the Lomé Convention(s) to the Cotonou Agreement.
Uso da modelagem multicritério para apoio ao decisor na alocação de produtos na Matriz Mercadológica do Ciclo de Vida dos Produtos
Authors: Sobral Marcos Felipe Falcao
Published: January 2014

A correta de alocação de produtos na matriz de ciclo de vida é de fundamental importância para as estratégias mercadológicas, operacionais e logísticas das organizações. Entretanto, os procedimentos de classificação dos produtos muitas vezes envolvem múltiplos critérios, que podem ser conflitantes entre si, e que precisam ser ponderados no momento da decisão. Isto torna a tarefa de classificação delicada e complexa. Em face disto, o presente trabalho visa propor o uso do método de apoio multicritério a decisão ELECTRE TRI como suporte no processo de alocação do portfólio de produtos na Matriz de Ciclo de Vida. Desde sua concepção o ELECTRE TRI tem sido aplicado com sucesso em diversos contextos empresariais, apresentado soluções estáveis adequadas ao problema. Seu uso na alocação de produtos na matriz de ciclo de vida proporcionará uma metodologia estruturada para realização desta tarefa, apoiando as empresas na análise e formação das estratégias empresariais.
Logística reversa – conceitos e implementação
Authors: Andrade Regiane Passariello , Junior Milton Vieira , Vanalle Rosangela Maria
Published: January 2014

A mudança de perfil das organizações e dos consumidores fez com que as organizações entendessem a importância de atividades ligadas à sustentabilidade e à preservação do meio ambiente. É necessário que as organizações entendam tanto os processos de logística de distribuição, como aqueles que envolvem a logística reversa, que é caracterizada pelo tratamento e destinação final dos produtos pós-consumo e pós-venda. A implementação da logística reversa apresenta forças propulsoras e forças restritivas que auxiliam e inibem sua implementação. O objetivo central deste trabalho é estudar as forças propulsoras e restritivas da logística reversa e, por meio de um estudo de caso realizado junto a uma empresa produtora de produtos de higiene, identificar se as práticas de logística reversa são aplicadas e de que forma, além da identificação da existência de indicadores de desempenho específicos. O estudo também investigou se a empresa considera a logística reversa uma questão estratégica.
Mères, militarisation et guerre
Authors: Cornut Jérémie , Turenne-Sjolander Claire
Published: January 2014

Le comportement socialement acceptable des mères endeuillées par la mort de leur enfant à la guerre est un enjeu politique de premier ordre, particulièrement dans les sociétés en guerre. Lorsque ces mères sont militarisées et qu’elles acceptent avec dignité et en silence leur deuil, elles sont un soutien à l’effort de guerre. Au contraire, si elles contestent la légitimité de la guerre et critiquent l’État pour la mort de leur enfant, elles sont une importante force antimilitariste. L’objectif de cet article est de voir dans quelle mesure la figure des mères de soldats est militarisée au Canada et au Québec. L’article repose, d’une part, sur une analyse de la place des mères endeuillées lors des cérémonies du jour du Souvenir. On s’y penche, d’autre part, sur la controverse qu’a provoquée la publication, par la Fédération des femmes du Québec, d’une capsule vidéo antimilitariste. La conclusion de cette étude est que les mères de soldats canadiennes sont militarisées. Tel est le cas au Québec également, en dépit de la tradition antimilitariste et pacifiste qui, pour certains, caractérise la société québécoise.
Rethinking Transediting
Authors: Schäffner Christina
Published: January 2014

This paper reflects on the terms used in investigating news translation, with a special focus on the term transediting as it was suggested in a paper by Stetting. After a summary of Stetting’s original arguments, some research into news translation is presented, illustrating main methods, findings, and concepts used. The paper presents arguments put forward by various scholars for using or rejecting the term translation for describing the complex processes of translation in the context of mass media and illustrates which alternative terms are used. It is shown that Stetting’s original aim in coining the term transediting was to raise awareness of translation being more than a pure replacement of a source text by an equivalent target text. Transformations as identified in news translation, however, are characteristic of translation more generally. Therefore, the paper finally reflects on whether there is a need to keep the term transediting and whether it has any explanatory power for describing the practices in news translation.
La primera agricultura Pitiusa y Balear: las evidencias de la Cova des Riuets
Authors: López Garí Josep Mª , Pérez Jordà Guillem , Marlasca Martín Ricard , Farrera Fernández Vanessa , Enrich Hoja Joan
Published: January 2014

Se presentan las evidencias relacionadas con las prácticas agrícolas de los primeros pobladores de Formentera halladas en las excavaciones de la cova des Riuets (La Mola, Formentera). La cueva conservaba un contexto de inicios del segundo milenio BC muy rico en restos cerámicos y orgánicos de todo tipo (fauna, ictiofauna, malacofauna, carbones, etc), entre los que destacan los carpológicos, dada la escasez de estos en los contextos prehistóricos baleares. Por otra parte también se encontraron fragmentos de las partes activas y pasivas de los molinos, que permiten acercarnos a su tipología y realizar analíticas que nos indiquen su funcionalidad.
MLTUNSOR: UN NOU MODEL DE SEGELL IBÈRIC PROCEDENT DE CA L’ESTRADA (CANOVELLES)
Authors: Ferrer i Jané Joan
Published: January 2014

En aquest treball es presenta una nova lectura d’un conjunt de segells ibèrics sobre doli procedents de Ca l’Estrada (Canovelles), un establiment rural del s. I aC, on hi figura l’antropònim mltunsor, composat per mltun i sor, que s’interpreta com el terrissaire productor del doli. Cal destacar que el formant mltun formaria parella amb el ja conegut nmltun contribuint a una millor caracterització del valor del signe m.
Grafits apareguts al jaciment ibèric del Vilar a als Testers de Fonstcaldes (Valls, Tarragona). La tècnica del carbó vegetal
Authors: Fabra Salvat Maria Ester , Burguete Recasens Samuel , Vilalta Ribé Enric
Published: January 2014

Nous grafits sobre àmfores.
Restos romanos en torno a la ermita de San Sebastián: nuevos indicios de la posta de Turres (La Font de la Figuera, València)
Authors: López Serrano David , Arasa i Gil Ferrán , García Borja Pablo , Madaria Escudero José Luis
Published: January 2014

El seguimiento arqueológico de unas obras ya iniciadas junto a la ermita de San Sebastián en La Font de la Figuera, ha permitido documentar estructuras de época romana altoimperial que identificamos como parte de la posta Turres, junto al trazado de la vía Augusta.
Characterization of midgap interface states at Al2O3/InAlN interface formed by atomic layer deposition
Authors: Akazawa Masamichi
Published: January 2014

The midgap interface state density of the Al2O3/In0.19Al0.81N interface formed by atomic layer deposition was investigated by photoassisted capacitance–voltage (C–V) measurement. The interface-state density was derived to be in the range of 1012 eV−1 cm−2 around the midgap. The hysteresis of the C–V curve increased as the irradiated photon energy increased beyond the threshold value of 1.8 eV. This threshold energy value coincided with the energy difference between the conduction band edge and the charge neutrality level E
CNL for In0.19Al0.81N, which indicated the density of interface states at around E
CNL to be below the detection limit.
A Large Number of Southern Short-Tailed Shrew, Blarina carolinensis, Skulls Recovered From a Single Discarded Bottle
Authors: Platt Steven G. , Rainwater Thomas R. , Miller Stanlee M.
Published: January 2014

The recovery of 25 southern short-tailed shrew (Blarina carolinensis) skulls from a single discarded bottle in Louisiana appears to be the largest number of Blarina ever found in one bottle and reported in the literature. Conservation concerns about the impact of discarded bottles on small mammal faunas seem justified and warrant investigation.
Janus Particles with Stimuli‐Responsive Properties
Authors: Synytska Alla , Ionov Leonid
Published: January 2014

Janus particles are characterized by different properties, such as color, charge, and functional groups at different sides. Owing to their complex behavior, Janus particles became a highly attractive research topic. Particularly, interesting groups of Janus particles are the ones that are sensitive to external signals such as change of temperature, pH, and light. These Janus particles are able to dynamically assemble/disassemble to forming very complex structures or reversibly/irreversibly change their shape by folding/bending. Recent progress in this fascinating field is discussed.
Gums, Industrial
Authors: BeMiller James N.
Published: January 2014

Gums are polymers that can form highly viscous dispersions or gels in solvents or swelling agents. The term “industrial gums” usually refers to polysaccharides and their derivatives. This article overviews the structure, source, preparation, classification, and properties of industrial gums, including algin, carboxymethylcellulose, carrageenan, furcellaran, guar, gum arabic, starch and starch derivatives, hydroxyethylcellulose, and xanthan. Particular focus is put on water‐soluble polymers as well as on the toxicity and biocompatibility of natural and derived gums. For each class of industrial gums, rheological properties and representative industrial applications are also discussed.
Meeting the radiative forcing targets of the representative concentration pathways in a world with agricultural climate impacts
Authors: Kyle Page , Müller Christoph , Calvin Katherine , Thomson Allison
Published: January 2014

This study assesses how climate impacts on agriculture may change the evolution of the agricultural and energy systems in meeting the end‐of‐century radiative forcing targets of the representative concentration pathways (RCPs). We build on the recently completed Inter‐Sectoral Impact Model Intercomparison Project (ISI‐MIP) exercise that has produced global gridded estimates of future crop yields for major agricultural crops using climate model projections of the RCPs from the Coupled Model Intercomparison Project Phase 5 (CMIP5). For this study we use the bias‐corrected outputs of the HadGEM2‐ES climate model as inputs to the LPJmL crop growth model, and the outputs of LPJmL to modify inputs to the GCAM integrated assessment model. Our results indicate that agricultural climate impacts generally lead to an increase in global cropland, as compared with corresponding emissions scenarios that do not consider climate impacts on agricultural productivity. This is driven mostly by negative impacts on wheat, rice, other grains, and oil crops. Still, including agricultural climate impacts does not significantly increase the costs or change the technological strategies of global, whole‐system emissions mitigation. In fact, to meet the most aggressive climate change mitigation target (2.6 W/m2 in 2100), the net mitigation costs are slightly lower when agricultural climate impacts are considered. Key contributing factors to these results are (a) low levels of climate change in the low‐forcing scenarios, (b) adaptation to climate impacts simulated in GCAM through inter‐regional shifting in the production of agricultural goods, and (c) positive average climate impacts on bioenergy crop yields.
Kelvin and Rossby‐gravity wave packets in the lower stratosphere of some high‐top CMIP5 models
Authors: Lott F. , Denvil S. , Butchart N. , Cagnazzo C. , Giorgetta M. A. , Hardiman S. C. , Manzini E. , Krismer T. , Duvel J.‐P. , Maury P. , Scinocca J. F. , Watanabe S. , Yukimoto S.
Published: January 2014

We analyze the stratospheric Kelvin and Rossby‐gravity wave packets with periods of a few days in nine high‐top (i.e., with stratosphere) models of the fifth Coupled Model Intercomparison Project (CMIP5). These models simulate realistic aspects of these waves and represent them better than the tropospheric convectively coupled waves analyzed in previous studies. There is nevertheless a large spread among the models, and those with a quasi‐biennial oscillation (QBO) produce larger amplitude waves than the models without a QBO. For the Rossby‐gravity waves this is explained by the fact that models without a QBO never have positive zonal mean zonal winds in the lower stratosphere, a situation that is favorable to the propagation of Rossby‐gravity waves. For the Kelvin waves, larger amplitudes in the presence of a QBO is counter intuitive because Kelvin waves are expected to have larger amplitude when the zonal mean zonal wind is negative, and this is always satisfied in models without a QBO. We attribute the larger amplitude to the fact that models tuned to have a QBO require finer vertical resolution in the stratosphere. We also find that models with large precipitation variability tend to produce larger amplitude waves. However, the effect is not as pronounced as was found in previous studies. In fact, even models with weak precipitation variability still have quite realistic stratospheric waves, indicating either that (i) other sources can be significant or that (ii) the dynamical filtering mitigates the differences in the sources between models.
Multimodel estimates of atmospheric lifetimes of long‐lived ozone‐depleting substances: Present and future
Authors: Chipperfield M. P. , Liang Q. , Strahan S. E. , Morgenstern O. , Dhomse S. S. , Abraham N. L. , Archibald A. T. , Bekki S. , Braesicke P. , Di Genova G. , Fleming E. L. , Hardiman S. C. , Iachetti D. , Jackman C. H. , Kinnison D. E. , Marchand M. , Pitari G. , Pyle J. A. , Rozanov E. , Stenke A. , Tummon F.
Published: January 2014

We have diagnosed the lifetimes of long‐lived source gases emitted at the surface and removed in the stratosphere using six three‐dimensional chemistry‐climate models and a two‐dimensional model. The models all used the same standard photochemical data. We investigate the effect of different definitions of lifetimes, including running the models with both mixing ratio (MBC) and flux (FBC) boundary conditions. Within the same model, the lifetimes diagnosed by different methods agree very well. Using FBCs versus MBCs leads to a different tracer burden as the implied lifetime contained in the MBC value does not necessarily match a model's own calculated lifetime. In general, there are much larger differences in the lifetimes calculated by different models, the main causes of which are variations in the modeled rates of ascent and horizontal mixing in the tropical midlower stratosphere. The model runs have been used to compute instantaneous and steady state lifetimes. For chlorofluorocarbons (CFCs) their atmospheric distribution was far from steady state in their growth phase through to the 1980s, and the diagnosed instantaneous lifetime is accordingly much longer. Following the cessation of emissions, the resulting decay of CFCs is much closer to steady state. For 2100 conditions the model circulation speeds generally increase, but a thicker ozone layer due to recovery and climate change reduces photolysis rates. These effects compensate so the net impact on modeled lifetimes is small. For future assessments of stratospheric ozone, use of FBCs would allow a consistent balance between rate of CFC removal and model circulation rate.
Micropattern Formation by Molecular Migration via UV‐induced Dehydration of Block Copolymers
Authors: Okada Kenji , Tokudome Yasuaki , Makiura Rie , Konstas Kristina , Malfatti Luca , Innocenzi Plinio , Ogawa Hiroki , Kanaya Toshiji , Falcaro Paolo , Takahashi Masahide
Published: January 2014

A novel UV lithographic technique for the patterning of the block copolymer (Pluronic) thin films is developed. The present method is based on UV‐induced water affinity changes in block copolymer films. By water vapor post‐treatment of the film, a difference in water content is established between UV illuminated and unilluminated sections, which can induce an osmotic pressure at the interface. This osmotic pressure drives the migration of Pluronic molecules, resulting in formation of patterns on the block copolymer films. Remarkably, this patterning method requires neither initiators nor polymerizable moieties which are essential for a conventional photolithographic approach. Additionally, the etching process is bypassed, eliminating the use of destructive acids or organic solvents and making this an environmentally friendly patterning protocol. It is reported that Pluronic is photo‐responsive to UV exposure, which causes the dehydration of the PEO‐PPO‐PEO backbone.
Reduction of nonspecific binding for cellular imaging using quantum dots conjugated with vitamin E
Authors: Pan Jie , Wan Dong , Bian Yuxia , Guo Yugao , Jin Fengmin , Wang Tuo , Gong Jinlong
Published: January 2014

Quantum dots (QDs) as luminescence probes play an important role in the field of life sciences and medicine in recent decades. However, hydrophobic QDs have many limitations in applications for biological imaging such as insolubility in aqueous solutions and nonspecific binding to cellular membranes and so on. This article describes the design and synthesis of d‐α‐tocopheryl polyethylene glycol 3350 succinate (TPGS3350)‐conjugated QDs (TPGS3350‐QDs) nanoparticles (NPs) for effective reduction of nonspecific cellular binding of QDs for biological imaging. TPGS3350 with n‐poly(ethylene glycol) (PEG)3350 group was used in order to enhance the stabilization and water solubility of QDs, and reduce nonspecific cellular binding of NPs with the function of long‐chain PEG3350. We have demonstrated that TPGS3350‐QDs NPs show good stability and dispersion in aqueous solutions and that small amount of TPGS3350‐QDs NPs were nonspecific bound with Michigan Cancer Foundation‐7 (MCF‐7) cells in comparison of mercaptoacetic acid‐coated QDs NPs, which confirmed TPGS3350 can efficiently reduce nonspecific cellular binding due to the effect of PEG3350 in TPGS3350. The nonspecific binding of TPGS3350‐QDs NPs was also found to be much lower than that of TPGS‐QDs NPs. The developed TPGS3350‐QDs NPs in this study could be a promising tool for molecular imaging such as in vivo cell trafficking studies. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1591–1597, 2014
Prenatal diagnosis of Carpenter syndrome: Looking beyond craniosynostosis and polysyndactyly
Authors: Victorine Anna S. , Weida Jennifer , Hines Karrie A. , Robinson Barrett , Torres‐Martinez Wilfredo , Weaver David D.
Published: January 2014

Carpenter syndrome is an autosomal recessive disorder comprising craniosynostosis, polysyndactyly, and brachydactyly. It occurs in approximately 1 birth per million. We present a patient with Carpenter syndrome (confirmed by molecular diagnosis) who has several unique and previously unreported manifestations including a large ovarian cyst and heterotaxy with malrotation of stomach, intestine, and liver. These findings were first noted by prenatal ultrasound and may assist in prenatally diagnosing additional cases of Carpenter syndrome. © 2014 Wiley Periodicals, Inc.
TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion
Authors: Palumbo Orazio , Fichera Marco , Palumbo Pietro , Rizzo Renata , Mazzolla Elisabetta , Cocuzza Donatella Maria , Carella Massimo , Mattina Teresa
Published: January 2014

Interstitial deletion of 2q24.2 is a rarely described cytogenetic aberration in patients with intellectual disability (ID). Previously reported genotype–phenotype correlation identified a minimum deleted region of 2.65 Mb including 15 genes. Recently, a patient with a de novo 2q24.2 microdeletion of 0.4 Mb encompassing only three genes was described. However, the precise relationship between most deleted genes and the clinical features remains unclear. Here we describe a 12‐year‐old male patient diagnosed with growth retardation and ID. He also showed microcephaly, right palpebral ptosis, scapular winging, and pectus excavatum. Single nucleotide polymorphisms (SNP) array analysis showed a de novo interstitial deletion of 0.122 Mb at 2q24.2 region harboring only TBR1 (T‐box, brain, 1; OMIM: 604616), which encodes a T‐box family transcription factor expressed in post‐mitotic projection neurons and functionally significant in embryologic corticogenesis. This is the first case of a deletion at 2q24.2 involving only TBR1. This finding narrows the smallest region of overlap (SRO) for deletions in this region and strengthens the previously suggested hypothesis that this gene is a strong candidate for the ID phenotype. The identification of TBR1 as candidate for ID encourages further molecular studies to identify novel mutations to understand the pathogenic effects of its haploinsufficiency. Finally, this report provides a review on 10 2q24.2 microdeletion patients. © 2014 Wiley Periodicals, Inc.
Proposed regulations for research with biospecimens: Responses from stakeholders at CTSA consortium institutions
Authors: Botkin Jeffrey R. , Anderson Rebecca , Murray Tom , Beskow Laura M. , Maschke Karen , Cuttler Leona
Published: January 2014

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects—including institutions in the NIH‐funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA‐funded institutions and CTSA‐affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions. © 2014 Wiley Periodicals, Inc.
A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma
Authors: Fujita Atsushi , Ochi Nobuhiko , Fujimaki Hidehiko , Muramatsu Hideki , Takahashi Yoshiyuki , Natsume Jun , Kojima Seiji , Nakashima Mitsuko , Tsurusaki Yoshinori , Saitsu Hirotomo , Matsumoto Naomichi , Miyake Noriko
Published: January 2014

Osteopathia striata with cranial sclerosis (OSCS) is an X‐linked dominant sclerosing bone dysplasia. Typically affected females show macrocephaly, characteristic facial appearance, cleft palate, mild learning difficulties, hearing loss, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis and scapulae. Typically affected males usually die at the fetal or early neonatal stage. Because of its variable expressivity, which ranges from asymptomatic to fetal death, clinical diagnosis of OSCS can be difficult. Here, we identify a unique female patient presenting with severe macrocephaly, characteristic facial appearance, developmental delay, and hepatoblastoma. Exome sequencing identified a novel de novo nonsense mutation (c.1045C>T, p.Glu349*) in the WTX gene associated with OSCS. The OSCS diagnosis was confirmed in this patient based on the hallmark appearance of longitudinal striations in long bones when viewed by X‐ray. WTX is also known as a tumor suppressor gene, and somatic mutations in that gene have been identified in Wilms tumors. In addition to this patient, although two patients with OSCS have been reported to have colorectal cancer or ovarian cancer, Wilms tumor has never been reported in association with this disorder. Tumor susceptibility in patients with OSCS is discussed. © 2014 Wiley Periodicals, Inc.
Germline CBL mutation associated with a noonan‐like syndrome with primary lymphedema and teratoma associated with acquired uniparental isodisomy of chromosome 11q23
Authors: Hanson Helen L. , Wilson Meredith J. , Short John P. , Chioza Barry A. , Crosby Andrew H. , Nash Ruth M. , Marks Karen J. , Mansour Sahar
Published: January 2014

Germline mutations in the gene CBL (Casitas B‐lineage lymphoma), involved in the RAS‐MAPK signaling pathway, have been found as a rare cause of the neuro‐cardio‐facial‐cutaneous syndromes. Somatically acquired homozygous CBL mutations were initially identified in association with myeloproliferative disorders, particularly juvenile myelomonocytic leukemia (JMML). We describe a girl with a Noonan‐like phenotype of bilateral ptosis, lymphedema of the lower limbs and moderate intellectual disability, due to a de novo heterozygous mutation in CBL. She developed an ovarian mixed germ cell/teratoma with later occurrence of mature liver, omental, and ovarian teratomas. Copy neutral loss of heterozygosity for the CBL mutation due to acquired segmental uniparental disomy of 11q23 was observed in three teratomas, suggesting a specific association of CBL mutations in germ cell tumor predisposition. © 2014 Wiley Periodicals, Inc.
A de novo 1.4‐Mb deletion at 21q22.11 in a boy with developmental delay
Authors: Fukai Ryoko , Hiraki Yoko , Nishimura Gen , Nakashima Mitsuko , Tsurusaki Yoshinori , Saitsu Hirotomo , Matsumoto Naomichi , Miyake Noriko
Published: January 2014

Monosomy 21 is a very rare chromosomal abnormality. At least 45 patients with partial deletion involving 21q11 have been reported. Here, we report a Japanese boy who presented with pre‐ and postnatal growth delays, psychomotor developmental delay, microcephaly, and iris coloboma. Cytogenetic analysis revealed a de novo 1.4‐Mb deletion at 21q22.11 containing 19 protein‐coding RefSeq genes. We compared the clinical phenotypes between the present patient and 16 previously reported patients with a deleted region associated with postnatal growth delay and psychomotor developmental delay. Interestingly, ITSN1 was the only gene deleted or disrupted in all cases; this gene is known to be associated with intellectual disability. Microcephaly and brain structural abnormalities including polymicrogyria and agenesis/hypoplasia of the corpus callosum may also result from haploinsufficiency of ITSN1, highlighting its clinical significance for the neurological features of patients with monosomy 21. © 2014 Wiley Periodicals, Inc.
A syndrome of facial dysmorphism, cubital pterygium, short distal phalanges, swan neck deformity of fingers, and scoliosis
Authors: Girisha Katta M. , Abdollahpour Hengameh , Shah Hitesh , Bhavani Gandham SriLakshmi , Graham John M. , Boggula Vijay Raju , Phadke Shubha R. , Kutsche Kerstin
Published: January 2014

We report on an adolescent girl with sparse scalp hair, wide columella extending below alae nasi, webbing at elbows, broad finger tips, short distal phalanx of fingers, swan neck deformity of fingers, scoliosis, tall vertebrae, short fibulae, short fourth metatarsal bone, abnormal distal humeri, and unilateral clubfoot at birth. The combination of these features represents a novel phenotype. We sequenced the protein‐coding regions of the FLNA and FLNB genes and did not observe any pathogenic sequence variation. Chromosomal microarray revealed a de novo copy number variation of uncertain clinical significance on 7p22.3. © 2014 Wiley Periodicals, Inc.
Tricho‐odonto‐onycho‐dermal dysplasia and WNT10A mutations
Authors: Kantaputra P. , Kaewgahya M. , Jotikasthira D. , Kantaputra W.
Published: January 2014

We report on three novel (IVS2+1G>A splice site, c.1066G>T, and c.1039G>T, and one previously reported (c.637G>A) WNT10A mutations in three patients affected with odonto‐onycho‐dermal dysplasia (OODD; OMIM 275980). OODD is a rare form of autosomal recessive ectodermal dysplasia involving hair, teeth, nails, and skin, characterized by hypodontia (tooth agenesis), smooth tongue with marked reduction of filiform and fungiform papillae, nail dysplasia, dry skin, palmoplantar keratoderma, and hyperhidrosis of palms and soles. The novel IVS+1G>A splice site mutation is predicted to cause significant protein alteration. The other novel mutations we found including c.1066G>T and c.1039G>T are predicted to cause p.Gly356Cys and p.Glu347X, respectively. Barrel‐shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. The name “tricho‐odonto‐onycho‐dermal dysplasia” is suggested to replace “odonto‐onycho‐dermal dysplasia” because hair anomalies including hypotrichosis and slow‐growing hair have been reported in numerous reported patients with this syndrome. © 2014 Wiley Periodicals, Inc.
A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract
Authors: Van Asbeck Ellyze , Wolthuis David F.G.J. , Mohamed Miski , Wevers Ron A. , Korenke Cristoph G. , Gardeitchik Thatjana , Morava Eva
Published: January 2014

Cutis laxa (CL) is a connective tissue disorder, characterized by loose, inelastic, sagging skin. Both acquired and inherited (dominant, recessive, and X‐linked) forms exist. Here, we describe a new phenotype, which overlaps with other known CL syndromes. Our patient has a unique combination of features in association with sagging, inelastic, wrinkled skin, including cataract, severe cardiomyopathy, abnormal fat distribution, improvement of skin‐wrinkling with age, and white matter abnormalities but no significant histologic collagen or elastin abnormalities. Mutation analysis of known CL genes was negative. We suggest that our patient has a novel syndrome, with the main features of CL, intellectual disability, abnormal fat distribution, cardiomyopathy, and cataract. © 2014 Wiley Periodicals, Inc.
Amyoplasia revisited
Authors: Hall Judith G. , Aldinger Kimberly A. , Tanaka Kimi I.
Published: January 2014

Amyoplasia is a specific type and the most common form of arthrogryposis (multiple congenital contractures). It is a clinical diagnosis at this time. Care should be used making the diagnosis because of the implications for recurrence, natural history, associated anomalies, and both etiology and pathogenesis. We reviewed over 600 published reports and 2,500 individual records to identify the 560 individuals reported here. Affected limbs had characteristic positions with fatty–fibrous replacement of muscle. Upper limb involvement was usually characterized by extended elbows. Lower limbs were held in various positions at birth; however, equinovarus positioning of feet was almost always present. Symmetric involvement was common. Among 560 affected individuals, subtypes were identified: four‐limb symmetric involvement (331/560 = 55.9%), severe involvement (41/560 = 7.3%), three‐limb involvement (27/560 = 4.8%), upper limb only Amyoplasia (ULA; 94/560 = 16.8%), and lower limb only Amyoplasia (LLA; 25/560 = 15.5%). Discordant monozygotic twinning was increased, occurring in 6.6% (37/560; OR 10.9). A variety of additional anomalies were seen, attributed to apparent vascular compromise. Gastrointestinal vascular compromise‐type anomalies were present in 9.1% (51/560), trunk muscle defects in another 2.7% (15/560), digit compromise in 12.1% (68/560), constriction rings in 4.3% (24/560), and perinatal long bone fractures in 10.5% (59/560). Although prenatal ultrasound became the standard of care in 1990, only about one quarter of affected pregnancies were diagnosed prenatally since 1990. Amyoplasia appears to be completely sporadic. Novel pathogenetic mechanisms for the congenital anomalies seen in Amyoplasia need to be identified. © 2014 Wiley Periodicals, Inc.
A case of Rubinstein‐Taybi syndrome and congenital neuroblastoma
Authors: de Kort Ellen , Conneman Nikk , Diderich Karin
Published: January 2014

© 2014 Wiley Periodicals, Inc.
Pneumothorax from subpleural blebs—A new association of sotos syndrome?
Authors: Balasubramanian Meena , Shearing Emma , Smith Kath , Chavasse R. , Taylor R. , Tatton‐Brown Katrina , Primhak Robert , Ugonna Kelechi , Parker Michael J.
Published: January 2014

We describe two unrelated patients with molecularly confirmed Sotos syndrome with multiple subpleural blebs and pneumothorax. We propose this as a new association. Patient 1 is a 3‐year‐old boy with a 1.9 Mb interstitial deletion of the long arm of chromosome 5, with breakpoints at q35.2 and q35.3, encompassing NSD1 and Patient 2 is a 9‐year‐old girl with a de novo truncating mutation within NSD1. Both patients presented with sudden onset dyspnea due to a unilateral pneumothorax: Patient 1 at the age of 18 months and Patient 2 at 9 years. In both, the pneumothorax recurred following removal of the chest drain and, on further investigations, multiple subpleural blebs were identified necessitating a pleurodesis and tissue resection. This is the first report of multiple subpleural blebs leading to pneumothorax in association with Sotos syndrome. Given the similar and unusual presentation in the two affected patients, we suggest that this may be a real association, albeit a rare one. While screening would not be advocated for such a rare association, we recommend that clinicians consider pneumothorax in patients with Sotos syndrome and sudden onset of dyspnea and are aware that it may be refractory to first line treatment. © 2014 Wiley Periodicals, Inc.
Highly Efficient Platinum Group Metal Free Based Membrane‐Electrode Assembly for Anion Exchange Membrane Water Electrolysis
Authors: Pavel Claudiu C. , Cecconi Franco , Emiliani Chiara , Santiccioli Serena , Scaffidi Adriana , Catanorchi Stefano , Comotti Massimiliano
Published: January 2014

Low‐temperature electricity‐driven water splitting is an established technology for hydrogen production. However, the two main types, namely proton exchange membrane (PEM) and liquid alkaline electrolysis, have limitations. For instance, PEM electrolysis requires a high amount of costly platinum‐group‐metal (PGM) catalysts, and liquid alkaline electrolysis is not well suited for intermittent operation. Herein we report a highly efficient alkaline polymer electrolysis design, which uses a membrane‐electrode assembly (MEA) based on low‐cost transition‐metal catalysts and an anion exchange membrane (AEM). This system exhibited similar performance to the one achievable with PGM catalysts. Moreover, it is very suitable for intermittent power operation, durable, and able to efficiently operate at differential pressure up to 3 MPa. This system combines the benefits of PEM and liquid alkaline technologies allowing the scalable production of low‐cost hydrogen from renewable sources.
Nahtlose Integration von Dosis‐Wirkungs‐basiertem Screening und Flusschemie: effiziente Erzeugung von Struktur‐Aktivitäts‐Beziehungen von β‐Sekretase(BACE1)‐Hemmern
Authors: Werner Michael , Kuratli Christoph , Martin Rainer E. , Hochstrasser Remo , Wechsler David , Enderle Thilo , Alanine Alexander I. , Vogel Horst
Published: January 2014

Die Arzneistoffentwicklung stellt ein vielfältiges Aufgabenfeld dar, welches als grundlegendes Element die Erzeugung von Struktur‐Aktivitäts‐Beziehungen (SAR) durch wiederholte chemische Synthese und biologische Aktivitätsbestimmung maßgeschneiderter Moleküle beinhaltet. Hier berichten wir über die Entwicklung eines Fluss‐basierten biochemischen Assays und seine nahtlose Einbindung in ein vollautomatisiertes System, bestehend aus flusschemischer Synthese, Aufreinigung und Quantifizierung in serieller Abfolge. Diese neuartige Synthese‐Screening‐Platform ermöglicht es, SAR‐Daten von β‐Sekretase‐Hemmern in einer bisher unerreichten Durchlaufzeit von 1 Stunde anstelle mehrerer Tage zu erhalten. Die vollständige Automatisierung und Einbindung industrielle Prozesse hat seit jeher zu Produktivitätssteigerung und Kosteneinsparungen geführt. Diese Studie zeigt, wie diese Konzepte angewandt auf die Erzeugung von SAR‐Daten, zu einem effizienteren Arzneistoffentwicklungsprozess führen können.
Nitrogen‐Doped Carbon Nanosheets with Size‐Defined Mesopores as Highly Efficient Metal‐Free Catalyst for the Oxygen Reduction Reaction
Authors: Wei Wei , Liang Haiwei , Parvez Khaled , Zhuang Xiaodong , Feng Xinliang , Müllen Klaus
Published: January 2014

Nitrogen‐doped carbon nanosheets (NDCN) with size‐defined mesopores are reported as highly efficient metal‐free catalyst for the oxygen reduction reaction (ORR). A uniform and tunable mesoporous structure of NDCN is prepared using a templating approach. Such controlled mesoporous structure in the NDCN exerts an essential influence on the electrocatalytic performance in both alkaline and acidic media for the ORR. The NDCN catalyst with a pore diameter of 22 nm exhibits a more positive ORR onset potential than that of Pt/C (−0.01 V vs. −0.02 V) and a high diffusion‐limited current approaching that of Pt/C (5.45 vs. 5.78 mA cm−2) in alkaline medium. Moreover, the catalyst shows pronounced electrocatalytic activity and long‐term stability towards the ORR under acidic conditions. The unique planar mesoporous shells of the NDCN provide exposed highly electroactive and stable catalytic sites, which boost the electrocatalytic activity of metal‐free NDCN catalyst.
Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System
Authors: Buckley Dennis L. , Crews Craig M.
Published: January 2014

Traditionally, biological probes and drugs have targeted the activities of proteins (such as enzymes and receptors) that can be readily controlled by small molecules. The remaining majority of the proteome has been deemed “undruggable”. By using small‐molecule modulators of the ubiquitin proteasome, protein levels, rather than protein activity, can be targeted instead, thus increasing the number of druggable targets. Whereas targeting of the proteasome itself can lead to a global increase in protein levels, the targeting of other components of the UPS (e.g., the E3 ubiquitin ligases) can lead to an increase in protein levels in a more targeted fashion. Alternatively, multiple strategies for inducing protein degradation with small‐molecule probes are emerging. With the ability to induce and inhibit the degradation of targeted proteins, small‐molecule modulators of the UPS have the potential to significantly expand the druggable portion of the proteome beyond traditional targets, such as enzymes and receptors.
Seamless Integration of Dose‐Response Screening and Flow Chemistry: Efficient Generation of Structure–Activity Relationship Data of β‐Secretase (BACE1) Inhibitors
Authors: Werner Michael , Kuratli Christoph , Martin Rainer E. , Hochstrasser Remo , Wechsler David , Enderle Thilo , Alanine Alexander I. , Vogel Horst
Published: January 2014

Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure‐activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow‐based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in‐line quantification of compound concentration. This novel synthesis‐screening platform enables to obtain SAR data on b‐secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process.
Effects of cooling temperature and aging treatment on the morphology of nano‐ and micro‐porous poly(ethylene‐co‐vinyl alcohol) membranes by thermal induced phase separation method
Authors: Chang Hsu‐Hsien , Beltsios Konstantinos , Chen Yih‐Hang , Lin Dar‐Jong , Cheng Liao‐Ping
Published: January 2014

Poly(ethylene‐co‐vinyl alcohol) (EVOH 32) / 1,3‐propanediol mixtures are processed by thermally induced phase separation for the formation of porous membranes. The crystallization line was determined both by the cloud‐point and DSC methods. Two precursor solution compositions, four quench temperatures and various aging times were explored. It is found possible to generate both polymer‐crystallization controlled morphologies (for high quenches and/or sufficiently aged dopes), especially globular microporous ones, and novel nano‐scale porous morphologies dominated by intra‐binodal phase separation (for low quenches and limited or no precursor solution aging). Structural characterization of the membranes was accomplished via application of scanning electron microscopy and wide angle X‐ray diffraction. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40374.