bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative modeling reveals the principles of multi-scale chromatin boundary formation in human nuclear organization
Authors: Moore Benjamin L , Aitken Stuart , Semple Colin A
Published: May 2015

Background

Interphase chromosomes adopt a hierarchical structure, and recent data have characterized their chromatin organization at very different scales, from sub-genic regions associated with DNA-binding proteins at the order of tens or hundreds of bases, through larger regions with active or repressed chromatin states, up to multi-megabase-scale domains associated with nuclear positioning, replication timing and other qualities. However, we have lacked detailed, quantitative models to understand the interactions between these different strata.

Results

Here we collate large collections of matched locus-level chromatin features and Hi-C interaction data, representing higher-order organization, across three human cell types. We use quantitative modeling approaches to assess whether locus-level features are sufficient to explain higher-order structure, and identify the most influential underlying features. We identify structurally variable domains between cell types and examine the underlying features to discover a general association with cell-type-specific enhancer activity. We also identify the most prominent features marking the boundaries of two types of higher-order domains at different scales: topologically associating domains and nuclear compartments. We find parallel enrichments of particular chromatin features for both types, including features associated with active promoters and the architectural proteins CTCF and YY1.

Conclusions

We show that integrative modeling of large chromatin dataset collections using random forests can generate useful insights into chromosome structure. The models produced recapitulate known biological features of the cell types involved, allow exploration of the antecedents of higher-order structures and generate testable hypotheses for further experimental studies.
Current achievements and future perspectives in whole-organ bioengineering
Authors: Peloso Andrea , Dhal Abritee , Zambon Joao P , Li Peng , Orlando Giuseppe , Atala Anthony , Soker Shay
Published: May 2015

Irreversible end-stage organ failure represents one of the leading causes of death, and organ transplantation is currently the only curative solution. Donor organ shortage and adverse effects of immunosuppressive regimens are the major limiting factors for this definitive practice. Recent developments in bioengineering and regenerative medicine could provide a solid base for the future creation of implantable, bioengineered organs. Whole-organ detergent-perfusion protocols permit clinicians to gently remove all the cells and at the same time preserve the natural three-dimensional framework of the native organ. Several decellularized organs, including liver, kidney, and pancreas, have been created as a platform for further successful seeding. These scaffolds are composed of organ-specific extracellular matrix that contains growth factors important for cellular growth and function. Macro- and microvascular tree is entirely maintained and can be incorporated in the recipient’s vascular system after the implant. This review will emphasize recent achievements in the whole-organ scaffolds and at the same time underline complications that the scientific community has to resolve before reaching a functional bioengineered organ.
Regulation of the survival and differentiation of hepatic stem/progenitor cells by acyclic retinoid
Authors: Kamiya Akihide
Published: May 2015

During embryonic liver development, hepatic stem/progenitor cells (HpSCs) have a high proliferative ability and bipotency to differentiate into hepatocytes and cholangiocytes. Retinoic acid is a derivative of vitamin A and is involved in the proliferation and differentiation of stem/progenitor cells in several tissues. However, whether retinoic acid regulates the characteristics of HpSCs in the normal liver is still unknown. A recent study has shown that acyclic retinoid regulates the survival and proliferation of HpSCs derived from mouse foetal liver. Acyclic retinoid suppressed the expansion of CD29+CD49f+ HpSCs through the induction of hepatocytic differentiation and progression of apoptosis.
Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection
Authors: Qiu Xue-Cheng , Jin Hui , Zhang Rong-Yi , Ding Ying , Zeng Xiang , Lai Bi-Qin , Ling Eng-Ang , Wu Jin-Lang , Zeng Yuan-Shan
Published: May 2015

Introduction

Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy. However, the low neural differentiation frequency of MSCs has limited its application. The present study attempted to explore whether the grafted MSC-derived neural-like cells in a gelatin sponge (GS) scaffold could maintain neural features or transdifferentiate into myelin-forming cells in the transected spinal cord.

Methods

We constructed an engineered tissue by co-seeding of MSCs with genetically enhanced expression of neurotrophin-3 (NT-3) and its high-affinity receptor tropomyosin receptor kinase C (TrkC) separately into a three-dimensional GS scaffold to promote the MSCs differentiating into neural-like cells and transplanted it into the gap of a completely transected rat spinal cord. The rats received extensive post-operation care, including cyclosporin A administrated once daily for 2 months.

Results

MSCs modified genetically could differentiate into neural-like cells in the MN + MT (NT-3-MSCs + TrKC-MSCs) group 14 days after culture in the GS scaffold. However, after the MSC-derived neural-like cells were transplanted into the injury site of spinal cord, some of them appeared to lose the neural phenotypes and instead transdifferentiated into myelin-forming cells at 8 weeks. In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons. And the injured host neurons were rescued, and axon regeneration was induced by grafted MSCs modified genetically. In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups.

Conclusion

Grafted MSC-derived neural-like cells in the GS scaffold can transdifferentiate into myelin-forming cells in the completely transected rat spinal cord.
Neoinnervation and neovascularization of acellular pericardial-derived scaffolds in myocardial infarcts
Authors: Gálvez-Montón Carolina , Fernandez-Figueras M. Teresa , Martí Mercè , Soler-Botija Carolina , Roura Santiago , Perea-Gil Isaac , Prat-Vidal Cristina , Llucià-Valldeperas Aida , Raya Ángel , Bayes-Genis Antoni
Published: May 2015

Engineered bioimplants for cardiac repair require functional vascularization and innervation for proper integration with the surrounding myocardium. The aim of this work was to study nerve sprouting and neovascularization in an acellular pericardial-derived scaffold used as a myocardial bioimplant. To this end, 17 swine were submitted to a myocardial infarction followed by implantation of a decellularized human pericardial-derived scaffold. After 30 days, animals were sacrificed and hearts were analyzed with hematoxylin/eosin and Masson’s and Gallego’s modified trichrome staining. Immunohistochemistry was carried out to detect nerve fibers within the cardiac bioimplant by using βIII tubulin and S100 labeling. Isolectin B4, smooth muscle actin, CD31, von Willebrand factor, cardiac troponin I, and elastin antibodies were used to study scaffold vascularization. Transmission electron microscopy was performed to confirm the presence of vascular and nervous ultrastructures. Left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume, end-diastolic volume, end-systolic volume, end-diastolic wall mass, and infarct size were assessed by using magnetic resonance imaging (MRI). Newly formed nerve fibers composed of several amyelinated axons as the afferent nerve endings of the heart were identified by immunohistochemistry. Additionally, neovessel formation occurred spontaneously as small and large isolectin B4-positive blood vessels within the scaffold. In summary, this study demonstrates for the first time the neoformation of vessels and nerves in cell-free cardiac scaffolds applied over infarcted tissue. Moreover, MRI analysis showed a significant improvement in LVEF (P = 0.03) and CO (P = 0.01) and a 43 % decrease in infarct size (P = 0.007).
Cooperative joint inversion of 3D seismic and magnetotelluric data: With application in a mineral province
Authors: Takam Takougang Eric M. , Harris Brett , Kepic Anton , Le Cuong V. A.
Published: May 2015

The integration of different geophysical data has the potential to provide more accurate estimate of subsurface rock properties. Several methodologies and attempts have been developed over the years with the objective of reducing exploration risk. We have developed a cooperative joint-inversion approach intended to facilitate recovery of acoustic impedance (AI) using seismic and magnetotelluric (MT) data. In this approach, the MT data provided a pathway for iteratively building large-scale low-frequency information content not directly recoverable from the seismic data themselves. The MT data provided complementary information to seismic, especially in seismically complex terrains such as overthrust belts, subbasalt and subsalt, carbonate reefs or for targets below deep cover containing limestone, concretionary layers, or basalt. On the other hand, the seismic data provided structural information necessary to derive accurate resistivity models from MT inversion and small-scale features during seismic impedance inversion. The connections between resistivity and the elastic property of rocks are obtained from petrophysical relationships derived from available borehole data, or if not available, from empirical relationships. We tested our technique on synthetic and field data. The application of cooperative joint inversion to 3D seismic and MT data sets acquired in a mineral province made it possible to recover AI distribution across a wide range of geologic environments. The resulting rock property images provided a direct link to geology that is exceedingly difficult, if not impossible, to extract from the individual data sets.
Low-frequency reflection-data augmentation by an inpainting method: 1D acoustic media
Authors: Lesage Anne-Cécile , Yao Jie , Hussain Fazle , Kouri Donald J.
Published: May 2015

The augmentation of low frequencies is an important problem for inverting seismic reflection data. Through an acoustic-scattering approach, we have characterized how the data down to zero frequency grows in importance with increasing depth and the size of the velocity contrast. We have developed a Hermite distributed approximation functional (HDAF) inpainting method that provides a least-squares fitting of the acoustic-reflection data down to zero frequency. The HDAF data fitting is applied to the first Born approximation for compact velocity contrasts (the top and bottom depth velocities are equal). Several fitting constraints are derived using a Taylor expansion of the reflection data near zero frequency. They provide a coupling with the first Born approximation of the velocity contrast. The method can be extended to the general geophysical case, in which the final velocity i.e., is different from the starting velocity (by use of the distorted-wave Born approximation). Numerical results for 1D test cases with synthetic data showed that, if the shortest wavelength for reflection data is larger than the range of missing wavelengths, then the coupled fitting reconstructs well the full low-wavenumber data down to the zero wavenumber. Thus, it allows the first Born approximation to produce satisfactory results for data that are missing the low-frequency range. The method can be extended to higher dimensional problems and is a viable technique to augment seismic data in the low-frequency range.
Measurements of elastic and electrical properties of an unconventional organic shale under differential loading
Authors: Woodruff W. F. , Revil A. , Prasad M. , Torres-Verdín C.
Published: May 2015

We have developed an experimental approach to simultaneously measure the stress dependence of ultrasonic wave velocities at 1 MHz, and therefore the components of the undrained elastic stiffness tensor, as well as the components of the complex conductivity tensor in the frequency range from 100 mHz to 10 Hz. We performed the experiments on a cylindrical core sample from the Haynesville Formation (porosity of approximately 0.08, bound water excluded, and clay content, mostly illite, approximately 30–40 wt%). We performed experiments under controlled confining and pore fluid pressures, achieving differential pressure states representative of autochthonous reservoir conditions. Directional measurements were made using independent acquisition arrays (piezoelectric crystals and nonpolarizing electrodes) distributed azimuthally on the core sample external surface, the bedding plane being along the axis of the cylindrical core sample. Ultrasonic waveforms were recorded on a high-resolution oscilloscope, and complex impedance spectra were recorded with a four-electrode acquisition system using an impedance meter with precision of 0.1 mrad. Experiments were repeated under drained and undrained conditions, over loading and unloading sequences for fully water-saturated conditions. Measurements show strong stress dependence on ultrasonic and complex conductivity measurements, which can be ascribed to the opening and closing of cracks within the samples. The data were used to estimate the anisotropic electrical and elastic effective pressure coefficients of the core sample, resulting in effective stress coefficients smaller than one for both elastic and electrical properties. These effective stress coefficients were also smaller for the electrical and acoustic properties once the cracks have closed. The anisotropy ratio for the components of the complex conductivity tensor was on the order of 30, whereas it was only 2 for the compressional components of the stiffness tensor ([Formula: see text]).
Discrete 3D fracture network extraction and characterization from 3D seismic data — A case study at Teapot Dome
Authors: Thachaparambil Manoj Vallikkat
Published: May 2015

Three-dimensional discrete fracture networks (DFNs) extracted from the seismic data of the Tensleep Formation at Teapot Dome successfully matched 1D fracture data from multiple boreholes within the area. The extraction process used four seismic attributes, i.e., variance, chaos, curvature, and spectral edge, and their multiple realizations to define seismic discontinuities that could potentially represent fractures within the Tensleep Formation. All of the potential fracture attributes were further enhanced using a fracture-tracking attribute for better extraction and analysis of seismic discontinuity surfaces and their network properties. A state-of-the-art discontinuity surface extraction and characterization workflow uniformly extracted and interactively characterized the seismic discontinuity surfaces and networks that correlate with borehole fracture data. Among the attributes, a fracture-tracking attribute cube created out of the high-resolution spectral-edge attribute provided the best match with the borehole fracture data from the Tensleep Formation. Therefore, the extracted discontinuity planes were classified as fractures and then characterized. The extracted fracture population also matched earlier published records of faults and fractures at Teapot Dome. Unlike the conventional method, which uses 1D borehole fracture data as primary input and 3D seismic data as a guide volume during DFN modeling, I used 3D seismic attributes as the primary data and the 1D borehole fracture data only for quality control. I also evaluated the power of converting seismic fracture attribute volumes into discrete surfaces and networks for effective correlation with 1D fracture logs from boreholes.
Interpreting azimuthal Fourier coefficients for anisotropic and fracture parameters
Authors: Downton Jonathan E. , Roure Benjamin
Published: May 2015

Amplitude variation with offset and azimuth (AVOAz) analysis can be separated into two separate parts: amplitude variation with offset (AVO) analysis and amplitude variation with azimuth (AVAz) analysis. Useful information about fractures and anisotropy can be obtained just by examining the AVAz. The AVAz can be described as a sum of sinusoids of different periodicities, each characterized by its magnitude and phase. This sum is mathematically equivalent to a Fourier series, and hence the coefficients describing the AVAz response are azimuthal Fourier coefficients (FCs). This FC parameterization is purely descriptive. The aim of this paper is to help the interpreter understand what these coefficients mean in terms of anisotropic and fracture parameters for the case of P-wave reflectivity using a linearized approximation. The FC representation is valid for general anisotropy. However, to gain insight into the significance of FCs, more restrictive assumptions about the anisotropy or facture system must be assumed. In the case of transverse isotropic media with a horizontal axis of symmetry, the P-wave reflectivity linearized approximation may be rewritten in terms of azimuthal FCs with the magnitude and phase of the different FCs corresponding to traditional AVAz attributes. Linear slip theory is used to show that the FCs can be interpreted similarly for the cases of a single set of parallel vertical fractures in isotropic media and in transverse isotropic media with a vertical axis of symmetry (VTI). The magnitude of the FCs depends on the fracture weakness parameters and the background media. For the case of vertical fractures in a VTI background, the AVOAz inverse problem is underdetermined, so extra information must be incorporated to determine how the weights are modified due to this background anisotropy. We evaluated this on a 3D data set from northwest Louisiana for which the main target was the Haynesville shale.
Galant Recitative Schemas
Authors: Sherrill Paul , Boyle Matthew
Published: May 2015

Italianate recitative of the eighteenth and early nineteenth centuries constituted a distinct musical language that coexisted with the familiar style of common practice music. In this article we propose a theory of that language (“galant recitative”), which we characterize in terms of a core vocabulary of fifteen melodic formulas. Appendix 1 presents a roster of these formulas, which captures a unique fingerprint of recitative, distinct from the comparable inventory of homophonic phrase schemas in Robert Gjerdingen’s Music in the Galant Style. These recitative schemas are defined in terms of characteristic melodic profiles, harmonic contexts, formal roles, and expressive associations. One representative schema, the “O cielo,” is used to demonstrate the musical features and range of variation characteristic of all recitative schemas. The formal associations of the schemas allow us to describe the basic phrase syntax of recitative, grouping the schemas into three broad formal roles: initiatory, medial, and closing. Appendix 2 demonstrates this formal model by analyzing the dramatic climax of Leonardo Vinci and Pietro Metastasio’s opera Artaserse (1730). Additionally, some schemas have focused semantic connotations and are used to mark such utterance types as questions and witticisms. The article concludes with an analysis of scenes from act 1 of Mozart’s Così fan tutte, which shows how sensitivity to manipulations of galant recitative schemas can reveal subtle effects of characterization and dramatic continuity.
Mersenne and the Art of Delivery
Authors: Redwood André
Published: May 2015

This article seeks to broaden our conventional historical account of the intersection between music and rhetoric by examining that intersection in the music-theoretical writings of Marin Mersenne (1588–1648). Mersenne’s discussion of rhetoric, found chiefly in his Harmonie universelle (1636–37), emphasizes delivery (pronuntiatio or actio) rather than style (elocutio) as the basis for comparing the two disciplines. As such, it offers a notable contrast to the more familiar analogies put forth by the German theorists who have tended to dominate our perspective. At the heart of Mersenne’s theorization is the notion that both musical performance and oratorical delivery share their foundations in the physical world of sound channeled through the vibrating vocal apparatus of the human body. Delivery is thus in principle amenable to the physical analysis that Mersenne so valued as a scientific thinker. This emphasis on the voice, moreover, lets him situate rhetoric in terms of the relationship between the voice and the soul, thus linking delivery with divinity. With both oratory and music being understood as specialized forms of sound production, music is shown to aid rhetoric just as much as rhetoric aids music—perhaps even more so. Since Mersenne locates the commonality between music and rhetoric in the human body, his theory attempts to define a rhetoric of emotional persuasion, rather than one of stylistic surface. Emotional persuasion is effected through vocal inflections, which he terms “accents of the passions.” Most important, for Mersenne these “accents” achieve their highest purpose when used for religious persuasion through preaching.
Generation of sensory hair cells by genetic programming with a combination of transcription factors
Authors: Costa Aida , Sanchez-Guardado Luis , Juniat Stephanie , Gale Jonathan E. , Daudet Nicolas , Henrique Domingos
Published: May 2015

Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration.
The atlas of mouse development eHistology resource
Authors: Graham Elizabeth , Moss Julie , Burton Nick , Armit Chris , Richardson Lorna , Baldock Richard
Published: May 2015

The Atlas of Mouse Development by Professor Mathew Kaufman is an essential text for understanding mouse developmental anatomy. This definitive and authoritative atlas is still in production and is essential for any biologist working with the mouse embryo, although the last revision dates back to 1994. Here, we announce the eHistology online resource that provides free access to high-resolution colour images digitized from the original histological sections (www.emouseatlas.org/emap/eHistology/index.php) used by Kaufman for the Atlas. The images are provided with the original annotations and plate numbering of the paper atlas and enable viewing the material to cellular resolution.
Developmental biology teaching - the importance of a practical approach
Authors: Mulley John F
Published: May 2015

The huge growth in knowledge in many areas of biological sciences over the past few decades has created a major dilemma for those of us in higher education, for not only must we adequately and efficiently convey these new facts and concepts to our students, we must also ensure that they understand and appreciate them.

The field of developmental biology has witnessed such a massive growth in knowledge since the mid-1980s, driven mainly by advances in cell and molecular biology, and the development of new imaging techniques and tools. Ensuring that students fully appreciate the four-dimensional nature of embryonic development and morphogenesis is a particular issue, and one that I argue can only be properly learned via direct exposure to embryos via laboratory practicals.
The differing approach to commercial litigation in the European Court of Justice and the courts of England and Wales I
Authors: Clarke Anthony
Published: May 2015

Article by Sir Anthony Clarke published in
Amicus Curiae - Journal of the Society for Advanced Legal
Studies. The Journal is produced by the Society for Advanced
Legal Studies at the Institute of Advanced Legal Studies,
University of London.
Age discrimination: the new Regulations
Authors: Sprack John
Published: May 2015

A summary of the principal changes
introduced by the Employment Equality (Age) Regulations 2006 as
they came into effect in England and Wales. Extracts from the
Regulations follow the commentary. Article by John Sprack
(Barrister, part-time Chairman of Employment Tribunals and author
of Tottel's Guide to the Age Discrimination Regulations 2006)
published in Amicus Curiae – Journal of the Society for Advanced
Legal Studies at the Institute of Advanced Legal Studies. The
Journal is produced by SALS at the IALS (Institute of Advanced
Legal Studies, School of Advanced Study, University of
London).
Employee participation under the cross-border mergers directive
Authors: Wooldridge Frank
Published: May 2015

Brief commentary considering interpretative difficulties raised by the European Union Directive 2005/56/EC of October 26, 2005 on Cross-Border Mergers of limited liability companies. Article by Dr Frank Wooldridge published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, University of London).
Intestacy and family provision claims on death
Authors: Cooke Elizabeth
Published: May 2015

Brief article by Professor Elizabeth Cooke,
Law Commissioner for England and Wales, commenting on a lecture
held at the IALS in November 2009 on Inheritance Law and the Law
Commission's consultancy. Published in Amicus Curiae – Journal of
the Society for Advanced Legal Studies at the Institute of
Advanced Legal Studies. The Journal is produced by SALS at the
IALS (Institute of Advanced Legal Studies, School of Advanced
Study, University of London).
Civil recovery and international issues in relation to restraint and confiscation
Authors: Mobedji Philip F.J.
Published: May 2015

This article is taken from a presentation
given at a seminar held at the IALS in 2009 on "Civil recoveries
and criminal confiscation: UK and EU interventions against
fraud". The author is a barrister and Senior Restraint and
Confiscation Lawyer, Serious Fraud Office. The article was
published in Amicus Curiae – Journal of the Society for Advanced
Legal Studies at the Institute of Advanced Legal Studies. The
Journal is produced by SALS at the IALS (Institute of Advanced
Legal Studies, School of Advanced Study, University of
London).
So you think becoming a barrister is difficult? Try the French Bar!
Authors: Montgomery John Warwick
Published: May 2015

A personal account by John Warwick
Montgomery (Professor Emeritus of Law and Humanities, University
of Bedfordshire and Distinguished Professor, Patrick Henry
College, Virgina, USA) describing the practice and procedures
involved in training as a lawyer in France and joining the French
Bar. Published in Amicus Curiae – Journal of the Society for
Advanced Legal Studies at the Institute of Advanced Legal
Studies. The Journal is produced by SALS at the IALS (Institute
of Advanced Legal Studies, School of Advanced Study, University
of London).
Civil interventions for tackling MTIC fraud: a UK perspective
Authors: Pope Steven , Stone Roderick
Published: May 2015

Article by Steven Pope and Roderick Stone
(HM Revenue and Customs) considering civil law intervention
options in UK and EU law for tackling Missing trader intra
community (MTIC) fraud. This article is taken from a presentation
given at a seminar held at the IALS in 2009 on "Civil recoveries
and criminal confiscation: UK and EU interventions against
fraud". Published in Amicus Curiae – Journal of the Society for
Advanced Legal Studies at the Institute of Advanced Legal
Studies. The Journal is produced by SALS at the Institute of
Advanced Legal Studies, School of Advanced Study, University of
London.
The German limited and silent partnership
Authors: Wooldridge Frank
Published: May 2015

A consideration by Dr Frank Wooldridge of the German limited partnership and the German silent partnership which have considerable economic importance as entities in German business law. Published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, University of London).
Recent developments in intellectual property law in Australia with some reference to the global economy
Authors: Crennan Susan
Published: May 2015

This paper by Susan Crennan, Justice of the
High Court of Australia, addresses developments in Australia in
intellectual property law, with some reference to the global
economy, and deals with two patent cases, two copyright cases and
a designs case. The paper was original presented as a lecture at
the Institute of Advanced Legal Studies and is published in
Amicus Curiae - Journal of the Society for Advanced Legal
Studies. The Journal is produced by the Society for Advanced
Legal Studies at the Institute of Advanced Legal Studies,
University of London.
The credit crunch: the collapse of Lehman Brothers - and a Hong Kong scheme to handle Lehman claims
Authors: Connerty Anthony
Published: May 2015

Anthony Connerty (Barrister and Chartered Arbitrator) looks at the Lehman collapse - considering the background to the collapse of Lehman Brothers investment bank, claims related to the collapse, an example of a credit crunch claim, a criminal prosecution and a Hong Kong mediation and arbitration scheme aimed at dealing speedily with Lehman Brothers-related claims. Versions of this article have been published in Hong Kong in the January 2010 edition of Asian Dispute Review and in London in the July 9, 2010 edition of New Law Journal. Published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, University of London).
Moving a company's COMI to achieve a restructuring: factors for consideration
Authors: Kaczor Anna
Published: May 2015

This article sets out the main factors for establishing a company's centre of main interests ("COMI") and considers what should be done in order to successfully move the COMI to another jurisdiction, particularly within the European Union. Published in Amicus Curiae – Journal of the Society for Advanced Legal Studies at the Institute of Advanced Legal Studies. The Journal is produced by SALS at the IALS (Institute of Advanced Legal Studies, School of Advanced Study, University of London).
Propaganda oder Autonomie?
Authors: Amelina Anna
Published: May 2015

In dieser Studie wird der strukturelle Wandel des russischen Fernsehens vom sowjetischen Status quo (1970-1985) bis zum Jahre 2005 untersucht. Dieser Medienwandel, der 1985/1986 beginnt und neben dem Fernsehen auch andere Medien umfasst, wird hier als Prozess der Erosion von Propaganda und der Ausdifferenzierung eines autonomen Mediensystems beschrieben. Dabei werden zwei Aspekte prominent hervorgehoben: die Bedeutung der medialen Globalisierungsprozesse für das entstehende Mediensystem und die Wechselbeziehung zwischen Medienstrukturen und den zunächst parteilichen, später staatlichen Kontrollmechanismen der Medien. Die in der Russischen Föderation trotz globaler Diffusion und Vernetzung der Fernsehorganisationen weiterhin populäre Idee, dass Medien ein notwendiges Instrument politischer Machtausübung sind, stellt daher eines der zentralen Bezugsprobleme der Studie dar.
Das aufgeklärte Kind
Authors: Sager Christin
Published: May 2015

Die Notwendigkeit, Kinder sexuell aufzuklären, wird spätestens seit dem 18. Jahrhundert nicht mehr in Frage gestellt. Dennoch herrscht Uneinigkeit über die Inhalte und die pädagogische Umsetzung der Aufklärung. Anhand von (west-)deutschen Sexualaufklärungsbüchern für Kinder und Familien (1950-2010) und der darin enthaltenen Konstruktionen von kindlicher Sexualität rekonstruiert Christin Sager den Wandel von gesellschaftlichen Normstrukturen und von pädagogischen Debatten über kindliche Sexualität und Aufklärungspraxis: Welche Familien- und Geschlechterkonstruktionen, sexuelle Normen und Diversitätsvorstellungen sowie Diskurse über sexualisierte Gewalt manifestieren sich in den Aufklärungsbüchern?
Digitale Datenbanken
Authors: Burkhardt Marcus
Published: May 2015

Wir leben längst nicht mehr nur im Informationszeitalter, sondern in der Ära von Big Data. In dieser steht die Datenbank gleichzeitig für die riesigen Erkenntnispotenziale von Informationssammlungen wie für die bedrohlichen Informationsexzesse der digitalen Medienkultur. Zudem bezeichnet der Begriff konkrete Technologien und Verfahren der Sammlung und Bereitstellung von digitalen Informationen. Zwischen diesen sehr unterschiedlichen Auffassungen gilt es, Datenbanken medientheoretisch zu verorten. Marcus Burkhardt zeichnet die Geschichte der Datenbanken nach und fragt, wie technische Verfahren der Verwaltung digitaler Informationen bedingen, was auf welche Weise in Datenbanken gefunden und durch sie gewusst werden kann.
Männlichkeiten in der Literatur
Authors: Tholen Toni
Published: May 2015

Die Veränderung des Verhältnisses zwischen den Geschlechtern hängt nicht zuletzt davon ab, ob sich gesellschaftlich und kulturell neue Vorstellungen von Männlichkeit herausbilden und alternative, nicht-hegemoniale Lebensformen möglich werden. Auch in der Literatur der letzten Jahrzehnte macht sich ein allmählicher Wandel im männlichen Selbstbild bemerkbar, den es literaturwissenschaftlich angemessen darzustellen gilt. Unter der doppelten Perspektive von Wandel und Beharrung untersucht Toni Tholen Konzepte von Männlichkeit zwischen solitärer Existenz, Ehe, Familie und Autorschaft in Texten von R.D. Brinkmann, R. Barthes, P. Handke, W.G. Sebald, A. Gorz bis zu M. Streeruwitz und K.O. Knausgård.
Zuschauer des Lebens
Authors: Sander Julia Catherine
Published: May 2015

Indifferenz, Mattigkeit, Passivität - literarische Figuren der 1990er und 2000er Jahre irritieren durch die distanzierte Zuschauerposition, mit der sie sich und dem Leben begegnen. Julia Sander macht dieses Phänomen zum Thema und stellt es in den Kontext der Diskussion um eine Reformulierung von Subjektivität nach der Postmoderne: In der Auseinandersetzung mit Texten von Christian Kracht, Judith Hermann, Katharina Hacker und Ulrich Peltzer zeigt sie neue kritische und ethische Perspektiven auf, die sie mit zeitgenössischen philosophischen Überlegungen zu Entfremdung und Subjektivität zusammenführt. Dabei gerät die ambivalente Spannung von Distanz und Einbindung ebenso in den Fokus wie Konturen neuer Ansätze von Engagement in der Gegenwartsliteratur.
Szenische Hermeneutik
Authors: Bohn Ralf
Published: May 2015

Szenische Hermeneutik fragt danach, wie Sinn entsteht, wenn Subjekte sich in sozialen Handlungen wechselseitig Autorschaft zuweisen. Sind mehrere Subjekte simultan präsent, muss über die Koordination von Sprechen und Zuhören, Aktion und Agitation szenisch verhandelt werden. Situativitäten verwandeln sich dann in Narrative: Präsenzen werden zu Erzählungen. Solche Verhandlung und Verwandlung wird als »Verstehen von Sinn« erklärt. Szenische Hermeneutik fragt demnach, wie ein Sinnangebot durch einen Anderen legitimiert und inszeniert ist. Sie argumentiert handlungspragmatisch, nicht vornehmlich semantisch. Ralf Bohn bezieht sich sowohl auf theologische und philosophische Positionen der Hermeneutik von Schleiermacher über Dilthey bis Gadamer und von Sartre bis Heidegger als auch auf aktuelle Präsenzauffassungen von Szenifikation, Bildlichkeit und Erzählung, wie sie etwa Freud, Winnicott und Lorenzer entwickelt haben. Im Zentrum der Analyse von Inszenierungsereignissen steht nicht das auf die Szene bezogene Raumproblem, sondern die Erfassung hermeneutischer Zeit.
Das Hegemonieprojekt der ökologischen Modernisierung
Authors: Krüger Timmo
Published: May 2015

Ökologische Modernisierung gilt als Leitprinzip zeitgemäßer Umweltpolitik. Die ökomodernen Kernforderungen nach »Sustainable Development« und »Green Economy« zielen auf eine fortschreitende Entwicklung, die um eine Nachhaltigkeitskomponente ergänzt werden soll. Anhand von Carbon Capture and Storage (CCS) fragt Timmo Krüger nach den aktuellen Dynamiken in den Kämpfen um die Hegemonie in der internationalen Klimapolitik. Er zeigt: Da CCS-Technologien auf der fossilen und zentralisierten Energieinfrastruktur basieren, spitzt sich hier die Frage zu, inwieweit es zur adäquaten Bearbeitung der ökologischen Krise einer umfassenden Transformation gesellschaftlicher Strukturen bedarf.
The Impact of Industry on Oncology Research and Practice
Authors: Moy Beverly , Jagsi Reshma , Gaynor Richard B. , Ratain Mark J.
Published: May 2015

Public scrutiny has increased over potential conflicts of interest among oncology researchers and providers. Given the increased prevalence and complexity of industry relationships, oncologists are increasingly faced with ethical challenges when navigating their financial relationships with industry. Oncologists are continually dealing with changing conflict of interest policies within academic centers and professional societies. With the recent passage of The Sunshine Act, oncologists are beginning to understand the repercussions of this new law. The consequences of the increasing use of direct-to-consumer advertising on patients with cancer are also unclear. Finally, industry's perspective on the evolution of these relationships is not clearly understood. This manuscript discusses issues related to industry's influence on oncology practice and research.
Approaches to Reduce the Long-Term Burden of Treatment-Related Complications in Survivors of Childhood Cancer
Authors: Armenian Saro H. , Kremer Leontien C. , Sklar Charles
Published: May 2015

Advances in diagnostics, treatment strategies, and supportive care have contributed to a marked improvement in outcomes for children with cancer. This has resulted in a growing number of long-term childhood cancer survivors. Currently there are over 360,000 individuals who are survivors of childhood cancer in the United States. However, treatment for patients with childhood cancer with chemotherapy, radiation, and/or hematopoietic stem cell transplantation can result in health-related complications that may not become evident until years after completion of treatment. As a result, several initiatives have been established to help standardize the surveillance for treatment-related late effects in childhood cancer survivors. This review highlights emerging concepts related to commonly reported late effects, such as subsequent malignant neoplasms, cardiovascular disease, and endocrinopathies. It also discusses relevant population-based screening strategies to mitigate the long-term health-related burden in vulnerable populations of survivors.
Metabolism and Oxidative Stress Response Pathways in Kidney Cancer: A Tale of Chance and Necessity
Authors: Sourbier Carole , Srinivasan Ramaprasad , Linehan W. Marston
Published: May 2015

Over 270,000 patients are affected with kidney cancer worldwide and 120,000 died from this disease in 2014. Over the last few decades, important progress has been made in our understanding of the genetic and molecular mechanisms underlying the growth of these tumors, which has led to improvement in patient care. Some of the most significant recent advances came from the increasing number of large datasets generated by bioinformatics (genomics, proteomics, etc.) and their integration to characterize the genetic and molecular factors responsible for kidney tumor development and survival. Interestingly, deregulated metabolism and oxidative stress pathways are commonly found in advanced-stage kidney tumors and are important factors to consider and potentially target when developing therapeutic approaches.
Systemic Treatment: Maintenance Compared with Holiday
Authors: Punt Cornelis J.A. , Simkens Lieke H.J. , Koopman Miriam
Published: May 2015

With the currently available cytotoxic and targeted drugs, metastatic colorectal cancer (mCRC) may be controlled by systemic treatment for a substantial period of time. However, many questions remain about the optimal use of drugs and duration of treatment. The feasibility of chemotherapy-free intervals has been studied in patients with mCRC treated with chemotherapy alone, but the results are conflicting. Current data show that oxaliplatin may be safely interrupted, but they do not allow a firm conclusion on the safety of a full treatment break of chemotherapy. For targeted therapy, continuous inhibition of intracellular signaling by prolonged administration would theoretically be beneficial for efficacy of treatment. Recent data support the use of maintenance treatment with chemotherapy and bevacizumab. No data on the optimal duration of treatment with anti-epidermal growth factor receptor (EGFR) agents are currently available.
Combating Acquired Resistance to Tyrosine Kinase Inhibitors in Lung Cancer
Authors: Lovly Christine M.
Published: May 2015

The prospective identification and therapeutic targeting of oncogenic tyrosine kinases with tyrosine kinase inhibitors (TKIs) has revolutionized the treatment for patients with non–small cell lung cancer (NSCLC). TKI therapy frequently induces dramatic clinical responses in molecularly defined cohorts of patients with lung cancer, paving the way for the implementation of precision medicine. Unfortunately, acquired resistance, defined as tumor progression after initial response, seems to be an inevitable consequence of this treatment approach. This brief review will provide an overview of the complex and heterogeneous problem of acquired resistance to TKI therapy in NSCLC, with a focus on EGFR-mutant and ALK-rearranged NSCLC. In vitro models of TKI resistance and analysis of tumor biopsy samples at the time of disease progression have generated breakthroughs in our understanding of the spectrum of mechanisms by which a tumor can thwart TKI therapy and have provided an important rationale for the development of novel approaches to delay or overcome resistance. Numerous ongoing clinical trials implement strategies, including novel, more potent TKIs and rational combinations of targeted therapies, some of which have already proven effective in surmounting therapeutic resistance.
Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer
Authors: Zardavas Dimitrios , Piccart-Gebhart Martine
Published: May 2015

High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.
Challenging the Treatment Paradigm for Advanced Renal Cell Carcinoma: A Review of Systemic and Localized Therapies
Authors: Bex Axel , Larkin James , Voss Martin
Published: May 2015

The current standard of care for the management of advanced renal cell carcinoma (RCC) revolves around systemic therapy with molecularly targeted agents. Over the last decade, a total of seven targeted drugs have been approved but, altogether, only exploit two molecular targets in this disease: the vascular endothelial growth factor (VEGF) axis and the mammalian target of rapamycin (mTOR). Introduction of these agents has markedly improved outcomes compared with those in the cytokine era, yet comparatively little progress has been made since registration of the first targeted therapeutics occurred 10 years ago. In this article, we review efforts to improve on this current treatment paradigm. We discuss novel targets in this disease and corresponding new agents under investigation. The article dedicates particular attention to targeted immunotherapeutics, which are rapidly emerging as a new category of interest in this disease. Last, we review current data supporting the use of surgical interventions to improve outcomes in patients with metastatic disease.
Emerging Role for Novel Immunotherapy Agents in Metastatic Renal Cell Carcinoma: From Bench to Bedside
Authors: Weinstock Matthew , McDermott David F.
Published: May 2015

Therapies that augment the antitumor immune response have been an established treatment modality for metastatic renal cell carcinoma (mRCC) since the 1980s. An improved understanding of the factors that limit the immune response to cancer have led to the development of novel therapeutic agents. Most notably, monoclonal antibodies that block the programmed death (PD)-1 immune checkpoint pathway have demonstrated encouraging antitumor activity against mRCC in phase I and II clinical trials. However, as monotherapy these agents are unlikely to offer substantial clinical benefit for the majority of patients with mRCC. Combination approaches and improvements in patient selection will be essential to enhance their efficacy and ensure the rational application of immunotherapy. This review summarizes the clinical and preclinical data that support the use of novel immunotherapies for mRCC and looks forward to future directions for this promising therapeutic strategy.