bluuebunny/crossref_metadata_2025 huggingface dataset:
Limits on Limitations: The Essence of Fundamental Rights in the EU
Authors: Lenaerts Koen
Published: September 2019

The concept of the essence of a fundamental right—set out in Article 52(1) of the Charter of Fundamental Rights of the European Union (the “Charter”)—operates as a constant reminder that our core values as Europeans are absolute. In other words, they are not up for balancing. As the seminal judgment of the Court of Justice of the European Union (the “CJEU”) in Schrems shows, where a measure imposes a limitation on the exercise of a fundamental right that is so intense and so comprehensive that it calls into question that right as such, that measure is incompatible with the Charter, as it deprives the right at issue of its essence. This is so without the need for a balancing exercise of competing interests, because a measure that compromises the very essence of a fundamental right is automatically disproportionate. Therefore, the present contribution supports the contention that in order for the concept of essence to function in a constitutionally meaningful way, both EU and national courts should apply the “respect-for-the-essence test” before undertaking a proportionality assessment.
The Essence of Rights: An Unreliable Boundary?
Authors: Tridimas Takis , Gentile Giulia
Published: September 2019

Article 52(1) of the EU Charter of Fundamental Rights lays down respect for the essence of right as one of the requirements that limitations on rights must respect. This provision is not innovative, as it formalizes into EU law the distinction between “core” and “periphery” of rights present in many national constitutions and in the ECJ and ECtHR case law. Nonetheless, the express reference to essence has given unprecedented resonance to that concept. Essence as the “limit of limits” has a Janus-like character. On the one hand, it pronounces that every fundamental right bears a minimum content which is ringfenced from interference by public and private actors. On the other hand, it stresses the malleability of rights and their social function. The core/periphery dichotomy reflects a balancing act moored in European legal tradition whose symbolism outperforms its utility as a judicial tool. This Article examines the essence clause of the Charter in light of the ECJ case law and the constitutional traditions of the Member States and assesses its role in the framework of fundamental rights protection in EU law. The Article first attempts a classification of rights limitations clauses in national constitutions, following which it discusses the interpretation of essence by the Spanish and the Italian Constitutional Courts. The Article then engages with a theoretical discussion of the concept of essence and examines the case law of the ECJ. Lastly, it looks at the limitations of the concept as a rights protection instrument in EU law.
The “Essence” of International Human Rights
Authors: Thielbörger Pierre
Published: September 2019

While the “essence” of EU fundamental rights has received much attention following the CJEU’s Schrems decision, the concept of “essence” remains much less examined in international human rights law. Nonetheless, a concept of “essence” for human rights can also be found in international law. This Article discusses different aspects of the “essence” concept in international human rights law, namely non-derogability, non-restrictability, and minimum core, in three steps. First, the Article looks at civil political rights and socioeconomic rights separately and identifies two different approaches to the concept of essence for each of the two categories: While for civil and political rights the concept of essence is mainly linked to the notions of non-derogability and non-restrictability, for socioeconomic rights, the concept refers mainly to the states’ obligation to guarantee an essential level of protection independent of their resource limitations. Second, the Article continues by reading the two approaches together and identifies certain elements of an overarching “essence” concept. Finally, the Article discusses the relationship between the CJEU’s “essence” jurisprudence and the related concepts in international law and concludes with two theses: First, international law deserves more attention when reflecting on the EU’s concept of essence. It equally employs concepts of “essence” and also informs the development and interpretation of EU law. Second, when engaging with the question of whether the EU law should draw lessons from its international counterpart on the notion of “essence,” one must contemplate drawbacks for EU law that the concept has presented for international law.
Outcomes of extended-spectrum beta-lactamases producing Enterobacteriaceae colonization among patients abdominal surgery patients
Authors: Apisarnthanarak Anucha , Kondo Sumalee , Mingmalairak Chatchai , Mahawongkajit Prasit , Juntong Jatupong , Limpavitayaporn Palin , Sriussadaporn Ekkapak , Tongyoo Assanee , Mundy Linda M.
Published: September 2019

Preoperative enteric screening for extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae was conducted in 360 patients prospectively observed for surgical site infection (SSI). ESBL colonization (adjusted odds ratio [aOR], 2.4) and dirty wound classification (aOR, 3.6) were associated with SSI; no association between carbapenem prophylaxis and reduction in SSI was detected.
Hairpin vortices and highly elongated flow structures in a stably stratified shear layer
Authors: Watanabe Tomoaki , Riley James J. , Nagata Koji , Matsuda Keigo , Onishi Ryo
Published: September 2019

Turbulent structures in stably stratified shear layers are studied with direct numerical simulation. Flow visualization confirms the existence of hairpin vortices and highly elongated structures with positive and negative velocity fluctuations, whose streamwise lengths divided by the layer thickness are $O(10^{0})$ and $O(10^{1})$, respectively. The flow at the wavelength related to these structures makes a large contribution to turbulent kinetic energy. These structures become prominent in late time, but with small buoyancy Reynolds numbers indicating suppression of turbulent mixing. Active turbulent mixing associated with the hairpin vortices, however, does occur. The structures and the vertical profile of the integral shear parameter show connections between stable stratified shear layers and wall-bounded shear flows.
Numerical investigation of nanofluid particle migration and convective heat transfer in microchannels using an Eulerian–Lagrangian approach
Authors: Sharaf Omar Z. , Al-Khateeb Ashraf N. , Kyritsis Dimitrios C. , Abu-Nada Eiyad
Published: September 2019

An Eulerian–Lagrangian modelling approach was employed in order to investigate the flow field, heat transfer and particle distribution in nanofluid flow in a parallel-plate microchannel, with a focus on relatively low Reynolds numbers ($Re\leqslant 100$). Momentum and thermal interactions between fluid and particle phases were accounted for using a transient two-way coupling algorithm implemented within an in-house code that tracked the simultaneous evolution of the carrier and particulate phases while considering timescale differences between the two phases. The inaccuracy of assuming a homogeneous particle distribution in modelling nanofluid flow in microchannels was established. In particular, shear rate and thermophoresis were found to play a key role in the lateral migration of nanoparticles and in the formation of particle depletion and accumulation regions in the vicinity of the channel walls. At low Reynolds numbers, nanoparticle distribution near the walls was observed to gradually flatten in the streamwise direction. On the other hand, for relatively higher Reynolds numbers, higher particle non-uniformities were observed in the vicinity of the channel walls. Furthermore, it was established that convective heat transfer between channel walls and the bulk fluid can either improve or deteriorate with the addition of nanoparticles, depending on whether the flow exceeded a critical Reynolds number of enhancement. It was also established that Brownian motion and thermophoresis had a major role in nanoparticle deposition on the channel walls. In particular, Brownian motion was the main deposition mechanism for nano-sized particles, whereas due to thermophoresis, nanoparticles were repelled away from channel walls. The result of the competition between the two is that deposition gradually increased along the streamwise direction.
Geophysical signature of a World War I tunnel-like anomaly in the Forni Glacier (Punta Linke, Italian Alps)
Authors: Francese R. G. , Bondesan A. , Giorgi M. , Picotti S. , Carcione J. , Salvatore M. C. , Nicolis F. , Baroni C.
Published: September 2019

Global warming and the associated glacier retreat recently revealed the entrance to an ice–rock tunnel, at an altitude of ~3600 m a.s.l., in the uppermost portion of the Forni Glacier in the Central Italian Alps. The tunnel served as an entrance to an Austro-Hungarian cableway station excavated in the rocks during the Great War just behind the frontline. A comprehensive geophysical survey, based on seismic and ground-penetrating radar profiling, was then undertaken to map other possible World War I (WWI) remains still embedded in the ice. The ice–rock interface was reconstructed over the entire saddle and in the uppermost portion of the glacier. A prominent linear reflector was surprisingly similar to the common response of buried pipes. The reflector orientation, almost longitudinal to the slope, does not seem to be compatible with a glacial conduit or with other natural features. Numerical simulations of a series of possible targets constrained interpretation to a partly water-filled rounded shape cavity. The presence of a preserved WWI tunnel connecting Mount Vioz and Punta Linke could be considered a realistic hypothesis. The Forni glacier could be still considered polythermal and comprised of cold ice without basal sliding in its top portion.
Incompressible analytical models for spinning-down pulsars
Authors: Giliberti E. , Antonelli M. , Cambiotti G. , Pizzochero P. M.
Published: September 2019

We study a class of Newtonian models for the deformations of non-magnetised neutron stars during their spin-down. All the models have an analytical solution which allows to easily grasp the dependence of the strain on the star’s main physical quantities, such as radius, mass, and crust thickness.

We first use the model proposed by Franco, Link, and Epstein that depicts the star as made of a fluid core and an elastic crust with the same density, to compare the response to a decreasing centrifugal force on stars having different masses and equations of state. We find that the strain angle is peaked at the equator and its maximum value decreases as a function of the mass.

Afterwards, we introduce a second, more refined, model in which the core and the crust have different densities, and the gravitational potential of the deformed body is self-consistently accounted for. The strain angle is still a decreasing function of the stellar mass, but now its maximum value is typically peaked at the poles and is larger (by a factor of four) than the corresponding value in the one-density model.

Finally, within the present analytic approach, we evaluate the impact of the Cowling approximation: when the perturbations of the gravitational potential are neglected, we find an underestimation of the centrifugal effect on the star, since the strain angle is about 40% of the one obtained with the complete model.
The emission and scintillation properties of RRAT J2325−0530 at 154 MHz and 1.4 GHz
Authors: Meyers B. W. , Tremblay S. E. , Bhat N. D. R. , Shannon R. M. , Ord S. M. , Sobey C. , Johnston-Hollitt M. , Walker M. , Wayth R. B.
Published: September 2019

Rotating Radio Transients (RRATs) represent a relatively new class of pulsar, primarily characterised by their sporadic bursting emission of single pulses on time scales of minutes to hours. In addition to the difficulty involved in detecting these objects, low-frequency (

$ \lt 300\,\text{MHz}$

) observations of RRATs are sparse, which makes understanding their broadband emission properties in the context of the normal pulsar population problematic. Here, we present the simultaneous detection of RRAT J2325−0530 using the Murchison Widefield Array (154 MHz) and Parkes radio telescope (

$1.4\,\text{GHz}$

). On a single-pulse basis, we produce the first polarimetric profile of this pulsar, measure the spectral index (

$\alpha={-2.2\pm 0.1}$

), pulse energy distributions, and present the pulse rates in the context of detections in previous epochs. We find that the distribution of time between subsequent pulses is consistent with a Poisson process and find no evidence of clustering over the

$\sim\!1.5\,\text{h}$

observations. Finally, we are able to quantify the scintillation properties of RRAT J2325−0530 at 1.4 GHz, where the single pulses are modulated substantially across the observing bandwidth, and show that this characterisation is feasible even with irregular time sampling as a consequence of the sporadic emission behaviour.
Are remitted affective disorders and familial risk of affective disorders associated with metabolic syndrome, inflammation and oxidative stress? – a monozygotic twin study
Authors: Ottesen Ninja Meinhard , Meluken Iselin , Frikke-Schmidt Ruth , Plomgaard Peter , Scheike Thomas , Fernandes Brisa S. , Berk Michael , Poulsen Henrik Enghusen , Kessing Lars Vedel , Miskowiak Kamilla , Vinberg Maj
Published: September 2019

Background

Metabolic syndrome (MetS) is associated with reduced life expectancy in patients with affective disorders, however, whether MetS also plays a role before the onset of affective disorder is unknown. We aimed to investigate whether MetS, inflammatory markers or oxidative stress act as risk factors for affective disorders, and whether MetS is associated with increased inflammation and oxidative stress.

Methods

We conducted a high-risk study including 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected), their unaffected co-twins (high-risk) and twins with no personal or family history of affective disorder (low-risk). Metabolic Syndrome was ascertained according to the International Diabetes Federation (IDF) criteria. Inflammatory markers and markers of oxidative stress were analyzed from fasting blood and urine samples, respectively.

Results

The affected and the high-risk group had a significantly higher prevalence of MetS compared to the low-risk group (20%v.15%v.2.5%,p= 0.0006), even after adjusting for sex, age, smoking and alcohol consumption. No differences in inflammatory and oxidative markers were seen between the three groups. Further, MetS was associated with alterations in inflammatory markers, and oxidative stress was modestly correlated with inflammation.

Conclusion

Metabolic syndrome is associated with low-grade inflammation and may act as a risk factor and a trait marker for affective disorders. If confirmed in longitudinal studies, this suggests the importance of early intervention and preventive approaches targeted towards unhealthy lifestyle factors that may contribute to later psychopathology.
Inattention in boys from low-income backgrounds predicts welfare receipt: a 30-year prospective study
Authors: Vergunst Francis , Tremblay Richard E. , Nagin Daniel , Zheng Yao , Galera Cedric , Park Jungwee , Beasley Elizabeth , Algan Yann , Vitaro Frank , Côté Sylvana M.
Published: September 2019

Background

Childhood disruptive behaviors are highly prevalent and associated with adverse long-term social and economic outcomes. Trajectories of welfare receipt in early adulthood and the association of childhood behaviors with high welfare receipt trajectories have not been examined.

Methods

Boys (n = 1000) from low socioeconomic backgrounds were assessed by kindergarten teachers for inattention, hyperactivity, aggression, opposition, and prosociality, and prospectively followed up for 30 years. We used group-base trajectory modeling to estimate trajectories of welfare receipt from age 19–36 years using government tax return records, then examined the association between teacher-rated behaviors and trajectory group membership using mixed effects multinomial regression models.

Results

Three trajectories of welfare receipt were identified: low (70.8%), declining (19.9%), and chronic (9.3%). The mean annual personal employment earnings (US$) for the three groups at age 35/36 years was $36 500 (s.d. = $24 000), $15 600 (s.d. = $16 275), and $1700 (s.d. = $4800), respectively. Relative to the low welfare receipt group, a unit increase in inattention (mean = 2.64; s.d. = 2.32, range = 0–8) at age 6 was associated with an increased risk of being in the chronic group (relative risk ratio; RRR = 1.16, 95% CI 1.03–1.31) and in the declining group (RRR = 1.13, 95% CI 1.03–1.23), after adjustment for child IQ and family adversity, and independent of other behaviors. Family adversity was more strongly associated with trajectories of welfare receipt than any behavior.

Conclusions

Boys from disadvantaged backgrounds exhibiting high inattention in kindergarten are at elevated risk of chronic welfare receipt during adulthood. Screening and support for inattentive behaviors beginning in kindergarten could have long-term social and economic benefits for individuals and society.
Transparency and participatory aspects of investor-state dispute settlement in the EU ‘new wave’ trade agreements
Authors: Lam Joanna , Ünüvar Güneş
Published: September 2019

This article scrutinizes the investment chapters in the new EU Free Trade Agreements from a transparency perspective. The article examines the claims that the dispute settlement mechanisms in the new treaties are sufficiently participatory and more transparent than their predecessors. Procedural standards related to confidentiality of proceedings shall be analysed in the context of existing transparency safeguards in investment arbitration. In addition to procedural guarantees of transparency, the article examines relevant substantive rules affecting participatory aspects of dispute settlement. Furthermore, the article discusses forum-shopping strategies of the parties in the field of investment-related disputes, including internal forum-shopping and parallel proceedings using different procedural mechanisms. In this context, lessons from other fields such as international commercial arbitration related to transparency (in cases in which public interest is present) are highlighted. The proposal for the establishment of an integrated, multilateral court for investment cases is also invoked.
A double obstacle model for pricing bi-leg defaultable interest rate swaps
Authors: CHEN XINFU , LIANG JIN
Published: September 2019

Two mathematical models under so-called intensity and structure frameworks to pricing a double defaultable interest rate swap are established. The default could happen or jump to a high probability in both fixed and floating parties on the predetermined boundaries. The models lead to a new and interesting mathematical problem. As the intensity approaches infinity in designated regions, the solutions of the intensity models converge to a solution of a structure-type model which is an initial value problem of a partial differential equation coupled with two obstacles problem in their restricted regions. According to the value of the fixed rate, three cases are discussed. The free boundary that determines the swap rate and the free boundaries that determine the earlier termination of the contract (due to counterparty’s default) are analysed.
Keeping up with the therapeutic advances in schizophrenia: a review of novel and emerging pharmacological entities
Authors: Krogmann Amanda , Peters Luisa , von Hardenberg Laura , Bödeker Katja , Nöhles Viktor B. , Correll Christoph U.
Published: September 2019

Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3antagonist/5-HT1Apartial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal®and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine’s efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.
Beyond public: architects, activists, and the design of akichi at Tokyo’s Miyashita Park
Authors: Cayer Aaron , Bender Catherine Tsukasa
Published: September 2019

Peppered with galleries, ateliers, and upscale designer boutiques, Tokyo’s Shibuya ward is often described as a commercial haven for Japan’s urban fashionistas and style-conscious visitors. Within it, a narrow park sits atop a 1960s parking structure that was once a refuge for nearly one hundred homeless city residents until most were forcibly removed in 2010 by city officials. Dozens of blue tarp tents, umbrellas, weathered shoes, and cherished belongings were discarded, and the people who had lived there were fenced out indefinitely. Although this striking contrast of urban socioeconomic disparity is one that characterises many cities across the globe, the juxtapositions in Shibuya have been made increasingly visible by strong cohorts of unrelenting activists who have ignited decades of discourse and scholarly debate about individual rights to cities, as well as the role and agency of architects in the designing of public spaces. This article combines participant observations of art activists, semi-structured and oral history interviews of homeless residents in Tokyo, as well as historical analysis, to examine these tensions as they have played out at Miyashita Park in Shibuya, including how perpetual redesigns of the park by architects and urban planners tasked with ‘re-activating’ the park in the 1960s, 2000s, and again in the late 2010s, have been vehemently opposed. More specifically, the article examines how a vocal group of art activists organised in opposition to the park’s most recent redesign efforts sponsored by Nike and the idea that such a public-private partnership could produce an inclusive public space. Instead, the activists worked to problematise the appropriateness of terms such as ‘public’ altogether. Through art installations, writing, impromptu concerts, sporting events, and protests that engaged with the politics of their own bodies, the activists turned to alternative genealogies and definitions of ‘public’ as a way to connect more particularly to Japanese urban form and to resist hegemonic and imported concepts of ‘public’ as reproduced and reinforced by architects often without challenge. By drawing on alternative terms, such as akichi, meaning ‘open land’, the activists argue for a different sense of spatial inclusivity than the supposedly universal democratic ideals associated with designs for public spaces in Tokyo.
The city as critical project – a poetics of collective life
Authors: Holm Lorens , McEwan Cameron
Published: September 2019

If you want to know what society looks like, look at our cities, look at their distribution of spaces, their scales, their densities. Look at how cities curate events. This article sketches the basis for architectural thinking on individual/collective social formations as read through the texts of Vitruvius and Freud with support from Aristotle, Arendt, and Lacan, in parallel with city projects by the rooms+cities studio, a Master’s-level design research unit at the University of Dundee, which is itself a collective project that begins with the close reading of canonic city plans in search of the collective body of knowledge that comprises the discipline and practice of architecture. Teaching may not be the only way to change built environment thinking but it is one way. Vittorio Gregotti reckoned that the schools were best placed to challenge establishment practices with avantgarde thought. We use architecture to think the relation between the individual and the collective, and thereby to make a space for politics and public life. This article is thus comprised of two arguments, one predominantly textual, the other graphic, of complementary weight and importance, that run side by side and occasionally cross or mingle.
GLOBALLY INDETERMINATE GROWTH PATHS IN THE LUCAS MODEL OF ENDOGENOUS GROWTH
Authors: Bella Giovanni , Mattana Paolo , Venturi Beatrice
Published: September 2019

This paper shows that global indeterminacy may characterize the three-dimensional vector field implied by the Lucas [(1988)Journal of Monetary Economics22, 3–42] endogenous growth model. To achieve this result, we demonstrate the emergence of a family of homoclinic orbits connecting the steady state to itself in backward and forward time, when the stable and unstable manifolds are locally governed by real eigenvalues. In this situation, we prove that if the saddle quantity is negative, and other genericity conditions are fulfilled, a stable limit cycle bifurcates from the homoclinic orbit. Orbits originating in a tubular neighborhood of the homoclinic orbit are then bound to converge to this limit cycle, creating the conditions for the onset of global indeterminacy. Some economic intuitions related to this phenomenon are finally explored.
Ein schwierig behandelbares Asthma bronchiale muss nicht ein schweres Asthma bronchiale sein
Authors: Nussbaumer-Ochsner Yvonne
Published: September 2019

Zusammenfassung. Dank neuer Biologika stehen Patienten mit einem «schwierig behandelbaren» Asthma bronchiale neue Therapieoptionen zur Verfügung. Vor dem Einsatz solcher Medikamente ist jedes «schwierig behandelbare» Asthma auf Faktoren zu überprüfen, die eine suffiziente Asthmakontrolle erschweren (z.B. ungenügende Inhalationstechnik, Compliance, anhaltende Allergenexposition) und Asthma-aggravierende Co-Morbiditäten (z.B. chronische Rhinitis, Reflux, Schlafapnoe) sollten gesucht und behandelt werden. Für das Verständnis des Wirkmechanismus der Biologika ist eine Phänotypisierung unerlässlich.
Essstörungen
Authors: Verbeek Dorothe , Petermann Franz
Published: September 2019

Zusammenfassung. Essstörungen wie Anorexia und Bulimia nervosa sowie die Binge-Eating-Störung sind zwar vergleichsweise seltene, jedoch schwere psychische Erkrankungen, die im Jugendalter beginnen. Vor allem die Anorexie führt zu gravierenden körperlichen und psychischen Beeinträchtigungen bei Kindern und Jugendlichen. Es werden die verschiedenen Formen von Essstörungen sowie deren Häufigkeit und Entstehungsbedingungen kurz beschrieben. Daneben wird auf die hohe Zahl von Kindern und Jugendlichen, die durch subklinische Esssprobleme und Figursorgen belastet sind, eingegangen. Zur Vorbeugung von Essstörungen werden schulische und internetbasierte Präventionsprogramme vorgestellt. Abschließend erfolgt eine kurze Einordnung unterschiedlicher verhaltenstherapeutisch und psychodynamisch ausgerichteter Therapieprogramme.
Verbesserung der Impuls- und Emotionsregulation bei Binge-Eating-Störungen
Authors: Legenbauer Tanja , Preuss Hanna
Published: September 2019

Zusammenfassung. Impulsivität beeinflusst die Verarbeitung von störungsspezifischen Reizen und die Handlungskompetenz hinsichtlich der Nahrungsaufnahme. Neuere Studien adressieren daher unterschiedliche Facetten impulsiven Erlebens und Verhaltens, um eine Reduktion von Essanfällen und des Körpergewichts bei der Binge-Eating-Störung (BES) zu erzielen. ImpulsE ist ein Therapieprogramm zur Verbesserung der Impuls- und Emotionsregulationsfertigkeiten, welches mit einem computergestützten nahrungsbezogenen Inhibitionstraining kombiniert und mit einer Standardbehandlung (TAU) verglichen wurde. N = 31 Personen mit BES nahmen teil (n = 22 ImpulsE, n = 9 TAU). Die Ergebnisse zeigten Verbesserungen in der nahrungsbezogenen Verhaltensinhibition und der allgemeinen Essstörungspathologie in beiden Gruppen, während sich die Anzahl von Essanfällen nur bei ImpulsE signifikant senkte. Die Ergebnisse stellen erste Hinweise auf die Wirksamkeit eines solchen Trainings dar. Eine Adaption an Jugendliche erscheint sinnvoll.
Significant Electric Field Perturbations in Low Latitude Ionosphere due to the Passage of Two Consecutive ICMEs During 6–8 September 2017
Authors: Rout Diptiranjan , Pandey Kuldeep , Chakrabarty D. , Sekar R. , Lu Xian
Published: September 2019

This investigation shows that the significant electric field disturbances in the dip‐equatorial ionosphere during the geomagnetic storm of 6–8 September 2017 are due to the passage of two consecutive interplanetary coronal mass ejections (ICMEs). During the passage of the first ICME sheath, a long duration (∼10 hr) prompt penetration (PP) event is operational in which 60‐min periodic component is found to be present in vertical drift as well as in equatorial electrojet, but the 45‐min periodicity, though present, is not significant in equatorial electrojet. On 8 September, the shock associated with the second ICME enhances theFregion vertical plasma drift to ∼150 m/s in the evening hours which is one of the highest vertical drift ever measured over Jicamarca. The same PP electric field causes unusually large enhancement of the equatorial electrojet strength to ∼135 nT in the early morning hours over the Philippine sector. The disturbance dynamo (DD) that follows the storm causes an upward vertical drift of ∼55 m/s during postmidnight hours over Jicamarca which is one of the highest observed. These unusually large electric field perturbations cause significant changes in theFregion plasma fountain. It is shown that these electric field perturbations cannot be accounted by PP/DD electric field associated with the geomagnetic storm only and significant contribution from substorm is conspicuous. Therefore, the present investigation highlights the need to evaluate the role of substorm in unusually large electric field perturbations over equatorial ionosphere.
Causes of death in preterm neonates (<33 weeks) born in tertiary care hospitals in India: analysis of three large prospective multicentric cohorts
Authors: Jain Kajal , Sankar M. Jeeva , Nangia Sushma , Ballambattu Vishnu Bhat , Sundaram Venkataseshan , Ramji Siddharth , Plakkal Nishad , Kumar Praveen , Jain Ashish , Sivanandan Sindhu , Vishnubhatla Sreenivas , Chellani Harish , Deorari Ashok , Paul Vinod K. , Agarwal Ramesh
Published: September 2019

Objective

To estimate the direct causes of mortality among preterm neonates <33 weeks’ gestation by examining three large multicentric, hospital-based datasets in India.

Method

Three prospective hospital-based datasets: National Neonatal Perinatal Database (NNPD) of India, Delhi Neonatal Infection Study (DeNIS) cohort, and Goat Lung Surfactant Extract (GLSE)-Plus cohort were analyzed to study the causes of death among preterm neonates of less than 33 weeks’ gestation admitted to the participating tertiary care hospitals in India.

Results

A total of 8024 preterm neonates were admitted in the three cohorts with 2691 deaths. Prematurity-related complications and sepsis contributed to 53.5% and 19.8% of deaths in the NNPD cohort, 51.0% and 25.0% in the DeNIS cohort, and 39.7% and 40.9% in GLSE-Plus cohort, respectively.

Conclusions

Nearly a quarter (20-40%) of preterm neonates less than 33 weeks’ gestation admitted to Indian NICUs died of sepsis. The study results have implications for health policies targeted to reduce the neonatal mortality rate in India.
EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma
Authors: Tan Yi-Hung Carol , Srivastava Saumya , Won Brian M. , Kanteti Rajani , Arif Qudsia , Husain Aliya N. , Li Hubert , Vigneswaran Wickii T. , Pang Ka-Ming , Kulkarni Prakash , Sattler Martin , Vaidehi Nagarajan , Mambetsariev Isa , Kindler Hedy L. , Wheeler Deric L. , Salgia Ravi
Published: September 2019

Squamous cell carcinoma (SCC) and malignant pleural mesothelioma (MPM) are thoracic malignancies with very poor prognosis and limited treatment options. It is an established fact that most of the solid tumors have overexpression of EPHA2 receptor tyrosine kinase. EPHA2 is known to exhibit opposing roles towards cancer progression. It functions in inhibiting cancer survival and migration via a ligand and tyrosine kinase dependent signaling (Y772). Whereas it is known to promote tumor progression and cell migration through a ligand-independent signaling (S897). We analyzed the expression profile and mutational status of the ephrin receptor A2 (EPHA2) in SCC and MPM cell lines and primary patient specimens. The EPHA2 receptor was found to be either overexpressed, mutated or amplified in SCC and MPM. In particular, the EPHA2 mutants A859D and T647M were interesting to explore, A859D Y772 dead mutant exhibited lower levels of phosphorylation at Y772 compared to T647M mutant. Molecular Dynamics simulations studies suggested that differential changes in conformation might form the structural basis for differences in the level of EPHA2 activation. Consequently, A859D mutant cells exhibited increased proliferation as well as cell migration compared to controls and T647M mutant. Kinomics analysis demonstrated that the STAT3 and PDGF pathways were upregulated whereas signaling through CBL was suppressed. Considered together, the present work has uncovered the oncogenic characteristics of EPHA2 mutations in SSC and MPM reinstating the dynamics of different roles of EPHA2 in cancer. This study also suggests that a combination of doxazosin and other EPHA2 inhibitors directed to inhibit the pertinent signaling components may be a novel therapeutic strategy for MPM and Non-small cell lung cancer patients who have either EPHA2 or CBL alterations.
Photo-editable macromolecular information
Authors: König Niklas Felix , Al Ouahabi Abdelaziz , Oswald Laurence , Szweda Roza , Charles Laurence , Lutz Jean-François
Published: September 2019

Light-induced alteration of macromolecular information plays a central role in biology and is known to influence health, aging and Darwinian evolution. Here, we report that light can also trigger sequence variations in abiotic information-containing polymers. Sequence-coded poly(phosphodiester)s were synthesized using four phosphoramidite monomers containing either photo-sensitive or photo-inert substituents. These monomers allow different sequence manipulations. For instance, using two light-cleavable monomers containing o-nitrobenzyl ether and o-nitroveratryl ether motifs, photo-erasable digital polymers were prepared. These polymers can be decoded by tandem mass spectrometry but become unreadable after UVA exposure. The opposite behavior, i.e. photo-revealable sequences, was obtained with polymers made of two isobaric monomers containing light-cleavable o-nitrobenzyl ether and light-inert p-nitrobenzyl ether substituents. Furthermore, when the latter two monomers were used in conjunction with a third monomer bearing a light-inert OH group, site-directed photo-mutations were induced in synthetic polymers. This was used herein to change the meaning of binary sequences.
Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions
Authors: Akula Murali K. , Ibrahim Mohamed X. , Ivarsson Emil G. , Khan Omar M. , Kumar Israiel T. , Erlandsson Malin , Karlsson Christin , Xu Xiufeng , Brisslert Mikael , Brakebusch Cord , Wang Donghai , Bokarewa Maria , Sayin Volkan I. , Bergo Martin O.
Published: September 2019

Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target proteins to membranes for GTP-loading. However, conditional deletion of GGTase-I in mouse macrophages increases GTP-loading of Rho proteins, leading to enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous deletion of the Rho family gene Rac1, but not Rhoa and Cdc42, reverses inflammation and arthritis in GGTase-I-deficient mice. Non-prenylated Rac1 has a high affinity for the adaptor protein Ras GTPase-activating-like protein 1 (Iqgap1), which facilitates both GTP exchange and ubiquitination-mediated degradation of Rac1. Consistently, inactivating Iqgap1 normalizes Rac1 GTP-loading, and reduces inflammation and arthritis in GGTase-I-deficient mice, as well as prevents statins from increasing Rac1 GTP-loading and cytokine production in macrophages. We conclude that blocking prenylation stimulates Rac1 effector interactions and unleashes proinflammatory signaling. Our results thus suggest that prenylation normally restrains innate immune responses by preventing Rac1 effector interactions.
The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation
Authors: Liebelt Frauke , Jansen Nicolette S. , Kumar Sumit , Gracheva Ekaterina , Claessens Laura A. , Verlaan-de Vries Matty , Willemstein Edwin , Vertegaal Alfred C. O.
Published: September 2019

In contrast to our extensive knowledge on ubiquitin polymer signaling, we are severely limited in our understanding of poly-SUMO signaling. We set out to identify substrates conjugated to SUMO polymers, using knockdown of the poly-SUMO2/3 protease SENP6. We identify over 180 SENP6 regulated proteins that represent highly interconnected functional groups of proteins including the constitutive centromere-associated network (CCAN), the CENP-A loading factors Mis18BP1 and Mis18A and DNA damage response factors. Our results indicate a striking protein group de-modification by SENP6. SENP6 deficient cells are severely compromised for proliferation, accumulate in G2/M and frequently form micronuclei. Accumulation of CENP-T, CENP-W and CENP-A to centromeres is impaired in the absence of SENP6. Surprisingly, the increase of SUMO chains does not lead to ubiquitin-dependent proteasomal degradation of the CCAN subunits. Our results indicate that SUMO polymers can act in a proteolysis-independent manner and consequently, have a more diverse signaling function than previously expected.
Asymmetric catalysis mediated by a mirror symmetry-broken helical nanoribbon
Authors: Shen Zhaocun , Sang Yutao , Wang Tianyu , Jiang Jian , Meng Yan , Jiang Yuqian , Okuro Kou , Aida Takuzo , Liu Minghua
Published: September 2019

Although chirality has been recognized as an essential entity for life, it still remains a big mystery how the homochirality in nature emerged in essential biomolecules. Certain achiral motifs are known to assemble into chiral nanostructures. In rare cases, their absolute geometries are enantiomerically biased by mirror symmetry breaking. Here we report the first example of asymmetric catalysis by using a mirror symmetry-broken helical nanoribbon as the ligand. We obtain this helical nanoribbon from a benzoic acid appended achiral benzene-1,3,5-tricarboxamide by its helical supramolecular assembly and employ it for the Cu2+-catalyzed Diels–Alder reaction. By thorough optimization of the reaction (conversion: > 99%, turnover number: ~90), the enantiomeric excess eventually reaches 46% (major/minor enantiomers = 73/27). We also confirm that the helical nanoribbon indeed carries helically twisted binding sites for Cu2+. Our achievement may provide the fundamental breakthrough for producing optically active molecules from a mixture of totally achiral motifs.
RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury
Authors: Zhu Xinzhou , Yan Jingyi , Bregere Catherine , Zelmer Andrea , Goerne Tessa , Kapfhammer Josef P. , Guzman Raphael , Wellmann Sven
Published: September 2019

Hypoxic ischemia (HI) is an acute brain threat across all age groups. Therapeutic hypothermia ameliorates resulting injury in neonates but its side effects prevent routine use in adults. Hypothermia up-regulates a small protein subset that includes RNA-binding motif protein 3 (RBM3), which is neuroprotective under stressful conditions. Here we show how RBM3 stimulates neuronal differentiation and inhibits HI-induced apoptosis in the two areas of persistent adult neurogenesis, the subventricular zone (SVZ) and the subgranular zone (SGZ), while promoting neural stem/progenitor cell (NSPC) proliferation after HI injury only in the SGZ. RBM3 interacts with IGF2 mRNA binding protein 2 (IMP2), elevates its expression and thereby stimulates IGF2 release in SGZ but not SVZ-NSPCs. In summary, we describe niche-dependent regulation of neurogenesis after adult HI injury via the novel RBM3-IMP2-IGF2 signaling pathway.
Bacterially synthesized tellurium nanostructures for broadband ultrafast nonlinear optical applications
Authors: Wang Kangpeng , Zhang Xiaoyan , Kislyakov Ivan M. , Dong Ningning , Zhang Saifeng , Wang Gaozhong , Fan Jintai , Zou Xiao , Du Juan , Leng Yuxin , Zhao Quanzhong , Wu Kan , Chen Jianping , Baesman Shaun M. , Liao Kang-Shyang , Maharjan Surendra , Zhang Hongzhou , Zhang Long , Curran Seamus A. , Oremland Ronald S. , Blau Werner J. , Wang Jun
Published: September 2019

Elementary tellurium is currently of great interest as an element with potential promise in nano-technology applications because of the recent discovery regarding its three two-dimensional phases and the existence of Weyl nodes around its Femi level. Here, we report on the unique nano-photonic properties of elemental tellurium particles [Te(0)], as harvest from a culture of a tellurium-oxyanion respiring bacteria. The bacterially-formed nano-crystals prove effective in the photonic applications tested compared to the chemically-formed nano-materials, suggesting a unique and environmentally friendly route of synthesis. Nonlinear optical measurements of this material reveal the strong saturable absorption and nonlinear optical extinctions induced by Mie scattering over broad temporal and wavelength ranges. In both cases, Te-nanoparticles exhibit superior optical nonlinearity compared to graphene. We demonstrate that biological tellurium can be used for a variety of photonic applications which include their proof-of-concept for employment as ultrafast mode-lockers and all-optical switches.
The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition
Authors: Oliveira-Mateos Cristina , Sánchez-Castillo Anaís , Soler Marta , Obiols-Guardia Aida , Piñeyro David , Boque-Sastre Raquel , Calleja-Cervantes Maria E. , Castro de Moura Manuel , Martínez-Cardús Anna , Rubio Teresa , Pelletier Joffrey , Martínez-Iniesta Maria , Herrero-Martín David , Tirado Oscar M. , Gentilella Antonio , Villanueva Alberto , Esteller Manel , Farré Lourdes , Guil Sonia
Published: September 2019

One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetalHMGA2gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogeneRPSAP52.RPSAP52is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation ofRPSAP52impairs the balance between the oncogeneLIN28Band the tumor suppressorlet-7family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels ofRPSAP52in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers.
Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains
Authors: Hao Yuxin , England Jeneffer P. , Bellucci Luca , Paci Emanuele , Hodges H. Courtney , Taylor Susan S. , Maillard Rodrigo A.
Published: September 2019

Cyclic nucleotide-binding (CNB) domains allosterically regulate the activity of proteins with diverse functions, but the mechanisms that enable the cyclic nucleotide-binding signal to regulate distant domains are not well understood. Here we use optical tweezers and molecular dynamics to dissect changes in folding energy landscape associated with cAMP-binding signals transduced between the two CNB domains of protein kinase A (PKA). We find that the response of the energy landscape upon cAMP binding is domain specific, resulting in unique but mutually coordinated tasks: one CNB domain initiates cAMP binding and cooperativity, whereas the other triggers inter-domain interactions that promote the active conformation. Inter-domain interactions occur in a stepwise manner, beginning in intermediate-liganded states between apo and cAMP-bound domains. Moreover, we identify a cAMP-responsive switch, the N3A motif, whose conformation and stability depend on cAMP occupancy. This switch serves as a signaling hub, amplifying cAMP-binding signals during PKA activation.
Direct evidence for grain boundary passivation in Cu(In,Ga)Se2 solar cells through alkali-fluoride post-deposition treatments
Authors: Nicoara Nicoleta , Manaligod Roby , Jackson Philip , Hariskos Dimitrios , Witte Wolfram , Sozzi Giovanna , Menozzi Roberto , Sadewasser Sascha
Published: September 2019

The properties and performance of polycrystalline materials depend critically on the properties of their grain boundaries. Polycrystalline photovoltaic materials – e.g. hybrid halide perovskites, copper indium gallium diselenide (CIGSe) and cadmium telluride – have already demonstrated high efficiencies and promise cost-effective electricity supply. For CIGSe-based solar cells, an efficiency above 23% has recently been achieved using an alkali-fluoride post-deposition treatment; however, its full impact and functional principle are not yet fully understood. Here, we show direct evidence for the passivation of grain boundaries in CIGSe treated with three different alkali-fluorides through a detailed study of the nanoscale optoelectronic properties. We determine a correlation of the surface potential change at grain boundaries with the open-circuit voltage, which is supported by numerical simulations. Our results suggest that heavier alkali elements might lead to better passivation by reducing the density of charged defects and increasing the formation of secondary phases at grain boundaries.