bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Sensitivity Analysis of Cost-Benefit Analysis Variables for Transport Interventions
Authors: JUHÁSZ Mattias , MÁTRAI Tamás
Published: August 2024

Cost-benefit analysis (CBA) is the universally applied tool to assess economic viability in assisting decisions on transport investments. Its framework is heavily influenced by the numerous variables it considers through estimating and valuing the intervention’s effects. This paper – utilising the authors’ previously implemented CBA test environment – comprehensively analyses the sensitivity of significant variables of three typical CBA models for transport interventions (road, rail and urban) to understand the prevailing appraisal approach better and to help focus on further methodological improvements. Morris and Sobol methods were selected to study the global sensitivity of and the relations between the input parameters of the models. The sensitivity test of the three analysed models provided similar results regarding which variables are most influential in CBAs. Input variables such as the investment cost, the economic discount rate, forecasted GDP changes and specific elasticities to these GDP changes often have a firm but mostly linear effect. Value of time, vehicle operating cost and mode choice-related parameters such as car availability, car occupancy rate, level of service indicators (e.g. frequency of service) and potential to induce travel demand (proxied by a ‘no travel’ parameter) are inputs with considerable linear effects and greater interactive effects.
Optimised LSTM Neural Network for Traffic Speed Prediction with Multi-Source Data Fusion
Authors: ZHAO Yongpeng , LI Yongcang , MA Changxi , WANG Ke , XU Xuecai
Published: August 2024

Predicting traffic speed accurately and in real-time is crucial for the development of smart transportation systems. Given the nonlinear and stochastic nature of vehicle data, integrating diverse spatio-temporal data sources with the Improved Particle Swarm Optimisation (IPSO) offers a promising approach to optimise the Long Short-Term Memory Neural Network (LSTM). Firstly, we enhance the optimisation capabilities of PSO by implementing nonlinear inertial weight and adaptive variation. Secondly, addressing the challenge of selecting the LSTM hyperparameters, the PSO algorithm effectively identifies global optimal solutions for hyperparameter optimisation, ensuring appropriate settings through iterative training. Subsequently, we conduct a case study using multi-source spatio-temporal traffic speed data, comparing our proposed IPSO-LSTM model with traditional neural network prediction models and advanced models. Results from the experiment demonstrate that the IPSO-LSTM model presented in this study addresses issues of parameter selection and inaccurate prediction encountered by traditional LSTM models in traffic state prediction. Moreover, it enhances the model’s ability to capture speed time series dynamics. Notably, in processing complex speed data, our model exhibits superior accuracy and stability in prediction.
Directed differentiation of functional corticospinal-like neurons from endogenous SOX6+/NG2+ cortical progenitors
Authors: Ozkan Abdulkadir , Padmanabhan Hari K , Shipman Seth L , Azim Eiman , Kumar Priyanka , Sadegh Cameron , Basak A Nazli , Macklis Jeffrey D
Published: August 2024

Corticospinal neurons (CSN) centrally degenerate in amyotrophic lateral sclerosis (ALS), along with spinal motor neurons, and loss of voluntary motor function in spinal cord injury (SCI) results from damage to CSN axons. For functional regeneration of specifically affected neuronal circuitry
in vivo
, or for optimally informative disease modeling and/or therapeutic screening
in vitro
, it is important to reproduce the type or subtype of neurons involved. No such appropriate
in vitro
models exist with which to investigate CSN selective vulnerability and degeneration in ALS, or to investigate routes to regeneration of CSN circuitry for ALS or SCI, critically limiting the relevance of much research. Here, we identify that the HMG-domain transcription factor
Sox6
is expressed by a subset of NG2+ endogenous cortical progenitors in postnatal and adult cortex, and that
Sox6
suppresses a latent neurogenic program by repressing inappropriate proneural
Neurog2
expression by progenitors. We FACS-purify these genetically accessible progenitors from postnatal mouse cortex and establish a pure culture system to investigate their potential for directed differentiation into CSN. We then employ a multi-component construct with complementary and differentiation-sharpening transcriptional controls (activating
Neurog2, Fezf2
, while antagonizing
Olig2
with
VP16:Olig2
). We generate corticospinal-like neurons from SOX6+/NG2+ cortical progenitors, and find that these neurons differentiate with remarkable fidelity compared with corticospinal neurons
in vivo
. They possess appropriate morphological, molecular, transcriptomic, and electrophysiological characteristics, without characteristics of the alternate intracortical or other neuronal subtypes. We identify that these critical specifics of differentiation are not reproduced by commonly employed
Neurog2
-driven differentiation. Neurons induced by
Neurog2
instead exhibit aberrant multi-axon morphology and express molecular hallmarks of alternate cortical projection subtypes, often in mixed form. Together, this developmentally-based directed differentiation from genetically accessible cortical progenitors sets a precedent and foundation for
in vitro
mechanistic and therapeutic disease modeling, and toward regenerative neuronal repopulation and circuit repair.
Transposon mutagenesis screen in Klebsiella pneumoniae identifies genetic determinants required for growth in human urine and serum
Authors: Gray Jessica , Torres Von Vergel L , Goodall Emily , McKeand Samantha A , Scales Danielle , Collins Christy , Wetherall Laura , Lian Zheng Jie , Bryant Jack A , Milner Matthew T , Dunne Karl A , Icke Christopher , Rooke Jessica L , Schneiders Thamarai , Lund Peter A , Cunningham Adam F , Cole Jeff A , Henderson Ian R
Published: August 2024

Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant K. pneumoniae infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections.
Interrogating basal ganglia circuit function in people with Parkinson’s disease and dystonia
Authors: Sumarac Srdjan , Spencer Kiah A , Steiner Leon A , Fearon Conor , Haniff Emily A , Kühn Andrea A , Hodaie Mojgan , Kalia Suneil K , Lozano Andres , Fasano Alfonso , Hutchison William Duncan , Milosevic Luka
Published: August 2024

Background:

The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.

Methods:

Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials.

Results:

GPi neurons were slower, burstier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.

Conclusions:

We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.

Funding:

This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).
Mutant mice lacking alternatively spliced p53 isoforms unveil Ackr4 as a male-specific prognostic factor in Myc-driven B-cell lymphomas
Authors: Fajac Anne , Simeonova Iva , Leemput Julia , Gabriel Marc , Morin Aurélie , Lejour Vincent , Hamon Annaïg , Rakotopare Jeanne , Vaysse-Zinkhöfer Wilhelm , Eldawra Eliana , Pinskaya Marina , Morillon Antonin , Bourdon Jean-Christophe , Bardot Boris , Toledo Franck
Published: August 2024

The
Trp53
gene encodes several isoforms of elusive biological significance. Here we show that mice lacking the
Trp53
Alternatively Spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in p53
+/+
Eμ-Myc males compared to p53
ΔAS/ΔAS
Eμ-Myc males, but also compared to p53
+/+
Eμ-Myc and p53
ΔAS/ΔAS
Eμ-Myc females. Pre-tumoral splenic cells from p53
+/+
Eμ-Myc males exhibited a higher expression of
Ackr4,
encoding an atypical chemokine receptor with tumor suppressive effects. We identified
Ackr4
as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of
ACKR4
increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.
Inversions Can Accumulate Balanced Sexual Antagonism: Evidence from Simulations and Drosophila Experiments
Authors: McAllester Christopher S , Pool John E
Published: August 2024

Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion associated with one haplotype can reduce the fitness load incurred by generating recombinant offspring, reinforcing its linkage to the haplotype and enabling both haplotypes to accumulate more antagonistic variants than expected otherwise. We develop and apply a forward simulator to examine these dynamics under a tradeoff between survival and male display. These simulations indeed generate inversion-associated haplotypes with opposing sex-specific fitness effects. Antagonism strengthens with time, and can ultimately yield karyotypes at surprisingly predictable frequencies, with striking genotype frequency differences between sexes and between developmental stages. To test whether this model may contribute to well-studied yet enigmatic inversion polymorphisms in
Drosophila melanogaster
, we track inversion frequencies in laboratory crosses to test whether they influence male reproductive success or survival. We find that two of the four tested inversions show significant evidence for the tradeoff examined, with
In(3R)K
favoring survival and
In(3L)Ok
favoring male reproduction. In line with the apparent sex-specific fitness effects implied for both of those inversions,
In(3L)Ok
was also found to be less costly to the viability and/or longevity of males than females, whereas
In(3R)K
was more beneficial to female survival. Based on this work, we expect that balancing selection on antagonistically pleiotropic traits may provide a significant and underappreciated contribution to the maintenance of natural inversion polymorphism.
The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system of daf-18/PTEN Caenorhabditis elegans mutants
Authors: Giunti Sebastián , Blanco María Gabriela , De Rosa María José , Rayes Diego
Published: August 2024

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including Autism Spectrum Disorders (ASDs).Mutations in PTEN, the main negative regulator of the PI3K/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the
C. elegans
neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that
daf-18
/
PTEN
mutations specifically impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The specific defects observed in the GABAergic system in
daf-18/PTEN
mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in
daf-18/PTEN
mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.
A single-cell atlas of the miracidium larva of Schistosoma mansoni reveals cell types, developmental pathways, and tissue architecture
Authors: Attenborough Teresa , Rawlinson Kate A , Diaz Soria Carmen L , Ambridge Kirsty , Sankaranarayanan Geetha , Graham Jennie , Cotton James A , Doyle Stephen R , Rinaldi Gabriel , Berriman Matthew
Published: August 2024

Schistosoma mansoni is a parasitic flatworm that causes the major neglected tropical disease schistosomiasis. The miracidium is the first larval stage of the life cycle. It swims and infects a freshwater snail, transforms into a mother sporocyst, where its stem cells generate daughter sporocysts that give rise to human-infective cercariae larvae. To understand the miracidium at cellular and molecular levels, we created a whole-body atlas of its ~365 cells. Single-cell RNA sequencing identified 19 transcriptionally distinct cell clusters. In situ hybridisation of tissue-specific genes revealed that 93% of the cells in the larva are somatic (57% neural, 19% muscle, 13% epidermal or tegument, 2% parenchyma, and 2% protonephridia) and 7% are stem. Whereas neurons represent the most diverse somatic cell types, trajectory analysis of the two main stem cell populations indicates that one of them is the origin of the tegument lineage and the other likely contains pluripotent cells. Furthermore, unlike the somatic cells, each of these stem populations shows sex-biased transcriptional signatures suggesting a cell-type-specific gene dosage compensation for sex chromosome-linked loci. The miracidium represents a simple developmental stage with which to gain a fundamental understanding of the molecular biology and spatial architecture of schistosome cells.
Laminar specificity and coverage of viral-mediated gene expression restricted to GABAergic interneurons and their parvalbumin subclass in marmoset primary visual cortex
Authors: Federer Frederick , Balsor Justin , Ingold Alexander , Babcock David P , Dimidschstein Jordane , Angelucci Alessandra
Published: August 2024

In the mammalian neocortex, inhibition is important for dynamically balancing excitation and shaping the response properties of cells and circuits. The various computational functions of inhibition are thought to be mediated by different inhibitory neuron types of which a large diversity exists in several species. Current understanding of the function and connectivity of distinct inhibitory neuron types has mainly derived from studies in transgenic mice. However, it is unknown whether knowledge gained from mouse studies applies to the non-human primate, the model system closest to humans. The lack of viral tools to selectively access inhibitory neuron types has been a major impediment to studying their function in the primate. Here, we have thoroughly validated and characterized several recently-developed viral vectors designed to restrict transgene expression to GABAergic cells or their parvalbumin (PV) subtype, and identified two types that show high specificity and efficiency in marmoset V1. We show that in marmoset V1 AAV-h56D induces transgene expression in GABAergic cells with up to 91-94% specificity and 79% efficiency, but this depends on viral serotype and cortical layer. AAV-PHP.eB-S5E2 induces transgene expression in PV cells across all cortical layers with up to 98% specificity and 86-90% efficiency, depending on layer. Thus, these viral vectors are promising tools for studying GABA and PV cell function and connectivity in the primate cortex.
Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis
Authors: Yang Luting , Hu Chunqing , Chen Xiaowen , Zhang Jie , Feng Zhe , Xiao Yanxin , He Weitai , Cui Tingting , Zhang Xin , Yang Yang , Zhang Yaling , Yan Yaping
Published: August 2024

Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a notoriously known rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.
Spatial localization of hippocampal replay requires dopamine signaling
Authors: Kleinman Matthew R , Foster David J
Published: August 2024

Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain’s reward or novelty signals is unknown. Here we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving male rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error, indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent reward prediction error signal that is reliable only in familiar environments.
Leaf litter nutrient content reveals benefits to traditional cropping systems in the Amazon
Authors: Brasil de Paula Erika Micheilla , da Cunha José Mauricio , Costa Campos Milton César , Campos Mantovanelli Bruno , Pinheiro da Silva Douglas Marcelo , Leite de Lima Alan Ferreira , Mendes Brito Wildson Benedito , Santana Macedo Rodrigo , Pereira de Oliveira Flávio
Published: August 2024

Soil fertility in the Amazon rainforest is very dependent to litter decomposition as a source of organic carbon and nutrients. Thus, land use that promote high litter decomposition might play a positive influence on soil chemical properties. The present study aimed to quantify the nutritional content of litter in anthropized and natural environments in Southern Amazonas. The study was conducted on two properties in the municipality of Canutama, in four areas: native forest, annatto, cupuassu, and guarana. In each area, 10 conical collectors (0.21 m²) were installed at a height of 0.3 m from the ground. The samples collected in each area for each month were dried in a forced circulation oven at 60ºC until reaching constant mass and weighed. Macro- and micronutrient content analyses were performed by sulfuric solubilization (N), nitric perchloric solubilization (Ca, Mg, P, K, Na, S, Cu, Fe, Mn, and Zn) and incineration (B). Variance analysis and comparison of means by Tukey test at the 5% probability level were applied to the data obtained, along with a multivariate analysis. This comparison was carried out by evaluating the overall average of a whole year of litter formation, as well as for formation within each month evaluated. Sulfur (S) was the only macronutrient that did not differ between environments (0.1 and 0.2 g kg-1). Macronutrients and micronutrient contents of litter (N: 16.92; Mg: 1.08; Cu: 16.00; Zn: 31.70; B: 104.40; g kg-1) were significantly highest in the annatto area. Annato also presents higher K (9.92 g kg-1) and P (0.70 g kg-1) contents. The litter of natural forest and guarana are richer in P (0.88 g kg-1) and Ca (g kg-1), respectively. Cupuassu litter showed lower nutritional contents, especially in macronutrients contents (N: 9.04; P: 0.51; K: 0.28; Ca: 0.76; Mg: 0.44; g kg-1). This indicates that traditional Amazonian agroecosystems may positively to improve quality of litter and impact nutrient cycling in soils highly weathered in the region.
Promising Insects for Sustainable Food and Biofuel
Authors: Kim Ji-Hyun , Kim Hye-Jin , Park Seul-Gi , Lim Seong-Rin
Published: August 2024

Food and energy security are global challenges due to growing demand for proteins and biofuels in the pursuit of a sustainable society. Although insects have emerged as environmentally-friendly sources that can replace meats, promising insect species as common resources for food and energy have not been examined. This study therefore identifies the insect species that can be utilized for sustainable food and energy based on their substance contents. These are nitrogen and phosphorus representing protein and minerals, respectively; lipids representing economic feasibility for biodiesel; and water representing drying energy requirement for storage. Fourteen species of the insects commonly farmed are examined: beetles, butterflies, cockroaches, flies, grasshoppers, and bees. Protaetia brevitarsis seulensis (PBS) larvae and termite are identified as promising species. The PBS larvae have the highest potential as a common resource for sustainable food and energy due to higher contents of nitrogen and phosphorus than beef, pork, and chicken; high oil content comparable to palm full fruit bunch (FFB) and soybean; and the lowest water content. This study can thus contribute to initiating new R&D and industrial endeavors to develop mass farming technology for such insects and securing sustainable resources for food and energy.
Immobiliengesellschaften gem. § 49 Abs. 1 Nr. 2 e) cc) EStG – Doppelbesteuerungsrisiken bei ausländischen Lebens- und Krankenversicherungen als Anteilseigner
Authors: Stadler Rainer , Beckmann Sophie
Published: August 2024

Der deutsche Immobilienmarkt stellt ein attraktives Ziel für ausländische Lebens- und Krankenversicherungen zur Anlage der Gelder ihrer Versicherungsnehmer dar. Während beim Erwerb von deutschen Immobilien häufig die grunderwerbsteuerlichen Aspekte im Fokus stehen, verdienen auch die ertragsteuerlichen Besonderheiten bei der Veräußerung besondere Beachtung. Insbesondere birgt die Veräußerung einer Immobilie durch eine Immobiliengesellschaft, an der ausländische Lebens- und Krankenversicherungen beteiligt sind, das Risiko einer wirtschaftlichen Doppelbesteuerung des Veräußerungsgewinns in Deutschland sowohl dem Grunde als auch der Höhe nach. Dieser Artikel erörtert die Umstände und rechtlichen Rahmenbedingungen, unter denen eine solche Doppelbesteuerung eintreten kann, und illustriert diese anhand von zwei Fallbeispielen eines französischen Lebensversicherungsunternehmens.
Der EuGH als Finanzgericht? — Zur besonderen Stellung des EuGH im und den besonderen Herausforderungen eines Vorabentscheidungsersuchen(s)
Authors: Hummel David
Published: August 2024

Ob der EuGH wirklich ein Finanzgericht ist, soll einmal mit einem großen Fragezeichen versehen werden. Was aber definitiv zu bejahen ist, ist eine starke Diskrepanz zwischen der Selbstwahrnehmung, d.h. wie der Gerichtshof selbst mit seinen Entscheidungen umgeht und sie verstanden wissen will, und der Wahrnehmung durch die deutsche Steuerrechtswissenschaft, d.h. wie dort mit seinen Entscheidungen umgegangen wird und wie sie dort recht häufig - bewusst oder unbewusst - missverstanden werden. Der Beitrag will die besondere Stellung des EuGH im Vorabentscheidungsersuchen und die besonderen Herausforderungen eines Vorabentscheidungsersuchens für den Gerichtshof näher beleuchten. Eine besondere Verantwortung trifft dabei die vorlegenden Gerichte, die durch die Qualität ihrer Vorabentscheidungsersuchen einen großen Einfluss auf die Qualität der Entscheidung des Gerichtshofs haben.
Observational evidence of the influence of Antarctic stratospheric ozone variability on middle atmosphere dynamics
Authors: Venkateswara Rao N. , Espy P. J. , Hibbins R. E. , Fritts D. C. , Kavanagh A. J.
Published: September 2015

Modeling results have suggested that the circulation of the stratosphere and mesosphere in spring is strongly affected by the perturbations in heating induced by the Antarctic ozone hole. Here using both mesospheric MF radar wind observations from Rothera Antarctica (67°S, 68°W) as well as stratospheric analysis data, we present observational evidence that the stratospheric and mesospheric wind strengths are highly anti‐correlated, and show their largest variability in November. We find that these changes are related to the total amount of ozone loss that occurs during the Antarctic spring ozone hole and particularly with the ozone gradients that develop between 57.5°S and 77.5°S. The results show that with increasing ozone loss during spring, winter conditions in the stratosphere and mesosphere persist longer into the summer. These results are discussed in the light of observations of the onset and duration of the Antarctic polar mesospheric cloud season.
The origin of water vapor rings in tropical oceanic cold pools
Authors: Langhans Wolfgang , Romps David M.
Published: September 2015

Tropical deep convection over the ocean is found to grow preferentially from thermodynamically preconditioned regions of high specific humidity and, thus, high moist static energy. For this reason, rings of enhanced specific humidity at the leading edges of evaporatively driven cold pools have recently received considerable attention. The prevailing theory explains these rings by the water vapor source from the evaporation of rain drops below cloud base. Their origin is studied in this letter using large‐eddy simulations of individual cumulus clouds that rise into a tropical atmosphere over ocean. It is demonstrated that—in contrast to this theory—water vapor rings are primarily explained by surface latent heat fluxes rather than by the evaporation of rain. This finding implies that conceptual models used in subgrid‐scale parameterizations of deep convection should consider the formation of rings of increased specific humidity by the cold‐pool‐induced enhancement of surface fluxes.
Clusters, deformation, and dilation: Diagnostics for material accumulation regions
Authors: Huntley Helga S. , Lipphardt B. L. , Jacobs Gregg , Kirwan A. D.
Published: September 2015

Clusters of material at the ocean surface have been frequently observed. Such accumulations of material play an important role in a variety of applications, from biology to pollution mitigation. Identifying where clusters will form can aid in locating, for example, hotspots of biological activity or regions of high pollutant concentration. Here cluster strength is introduced as a new metric for defining clusters when all particle positions are known. To diagnose regions likely to contain clusters without the need to integrate millions of particle trajectories, we propose to use dilation, which quantifies area changes of Lagrangian patches. Material deformation is decomposed into dilation and area‐preserving stretch processes to refine previous approaches based on finite‐time Lyapunov exponents (FTLE) by splitting the FTLE into fundamental kinematic properties. The concepts are developed theoretically and illustrated in the context of a state‐of‐the‐art data‐assimilating predictive ocean model of the Gulf of Mexico. Regions of dilation less than one are shown to be much more likely (6 times more likely in the given example) to be visited by particles than those of dilation greater than one. While the relationship is nonlinear, dilation and cluster strength exhibit a fairly good correlation. In contrast, both stretch and Eulerian divergence are found to be uncorrelated with cluster strength. Thus, dilation maps can be used as guides for identifying cluster locations, while saving some of the computational cost of trajectory integrations.
Upper ocean response and feedback to spring weather over the Kuroshio in the East China Sea: A coupled atmosphere‐ocean model study
Authors: Kueh Mien‐Tze , Lin Pay‐Liam
Published: September 2015

This study investigated the air‐sea interaction over the Kuroshio in the East China Sea by focusing on the response and feedback of the ocean to typical spring weather events. The Weather Research and Forecasting Model was coupled with the HYbrid Coordinate Ocean Model for use in the study. The study period comprised a sequence of typical weathers in the area: prevailing southwesterly winds, the passage of a cold front and the ensuing cold‐air outbreak, and the development of a Taiwan low. The air‐sea interaction operated on a diurnal time scale under conditions of moderate wind speeds, high insolation, and a shallow oceanic mixed layer. The sea surface temperature and upper ocean heat content increased progressively prior to the frontal passage. The model reproduced the retreat of Kuroshio in response to the strong wind during the cold‐air outbreak. The diurnal cycle vanished at high wind speeds. Wind stirring eroded the upper seasonal thermocline and deepened the oceanic mixed layer. The upper ocean heat content decreased because of entrainment cooling and surface heat losses. Surface restratification was subsequently suppressed in the thick and weakly stratified remnant layer. The consequently insufficient recovery of upper ocean heat content may have preconditioned a stagnation of the Taiwan low. The recovery of upper ocean heat content was discussed to derive the implication for climate simulations.
BN–Graphene Composites Generated by Covalent Cross‐Linking with Organic Linkers
Authors: Kumar Ram , Gopalakrishnan K. , Ahmad Irshad , Rao C. N. R.
Published: September 2015

Composites of boron nitride (BN) and carboxylated graphene are prepared for the first time using covalent cross‐linking employing the carbodiimide reaction. The BN1–xGx (x ≈ 0.25, 0.5, and 0.75) obtained are characterized using a variety of spectroscopic techniques and thermogravimetric analysis. The composites show composition‐dependent electrical resistivity, the resistivity decreasing with increase in graphene content. The composites exhibit microporosity and the x ≈ 0.75 composite especially exhibits satisfactory performance with high stability as an electrode in supercapacitors. The x ≈ 0.75 composite is also found to be a good electrocatalyst for the oxygen reduction reaction in fuel cells.
A Universal and Facile Approach for the Formation of a Protein Hydrogel for 3D Cell Encapsulation
Authors: Chen Yin , Dai Xin , Huang Lu , Sun Yang , Chan Ho N. , Shen Bo , Zeng Xiaoqian , Wu Zhenguo , Hsing I‐Ming , Guo Zhihong , Wu Hongkai
Published: September 2015

A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol‐containing crosslinkers via thiol‐ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin‐related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl‐glycyl‐aspartic acid (RGD)‐containing peptide into the system, thus warranting a bright future of it in regenerative medicine.
PEDOT:PSS Films with Greatly Enhanced Conductivity via Nitric Acid Treatment at Room Temperature and Their Application as Pt/TCO‐Free Counter Electrodes in Dye‐Sensitized Solar Cells
Authors: Yeon Changbong , Yun Sun Jin , Kim Jumi , Lim Jung Wook
Published: September 2015

A room‐temperature HNO3 treatment method is developed that significantly enhances the conductivity of a poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) film, which is one of the most promising transparent conducting materials. The PEDOT:PSS film treated with HNO3 exhibits a conductivity as high as 4100 S cm−1, which is the highest value among reported conductivities achieved by treatments at room temperature. The mechanism of this conductivity enhancement is elucidated by means of electrical, optical, structural, and compositional characterizations of the PEDOT:PSS films. The HNO3 treatment induces phase separation and crystallization in the (100) and (200) directions of PEDOT:PSS through selective removal of the PSS domains. This rearrangement significantly increases the conductivity through an enhancement of the inter‐chain interaction between the conducting polymers. Dye‐sensitized solar cells (DSSCs) that adopt these films as counter electrodes are developed as an example of practical applications. Using the HNO3‐treated PEDOT:PSS films, a power‐conversion efficiency of 8.59% is achieved for Pt/fluorine‐doped tin oxide (FTO)‐free DSSCs. This study demonstrates that a facile HNO3 treatment at room temperature is one of the most promising methods for obtaining highly conductive and transparent PEDOT:PSS films, and it facilitates the commercial use of PEDOT:PSS in next‐generation transparent electrodes.
Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities
Authors: Watanabe Yuko , Shido Kosuke , Niihori Tetsuya , Niizuma Hidetaka , Katata Yu , Iizuka Chie , Oba Daiju , Moriya Kunihiko , Saito‐Nanjo Yuka , Onuma Masaei , Rikiishi Takeshi , Sasahara Yoji , Watanabe Mika , Aiba Setsuya , Saito Ryuta , Sonoda Yukihiko , Tominaga Teiji , Aoki Yoko , Kure Shigeo
Published: September 2015

Genetic mosaicism for somatic mutations of oncogenes is common in genodermatoses, which can be complicated with extra‐cutaneous abnormalities. Here we describe an infant with a congenital anaplastic astrocytoma, a linear syringocystadenoma papilliferum, and ocular abnormalities. The BRAF c.1799T>A p.V600E mutation was detected in both the brain and skin tumor cells but not in the blood or normal skin cells, suggesting somatic mosaicsism for the mutation. Clinically, the brain tumor gradually became life threatening without any response to conventional chemotherapies including carboplatin, etoposide, and temozolomide. Vemurafenib, a BRAF p.V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single‐agent therapy was dramatically effective against the anaplastic astrocytoma; the tumor regressed, the cerebrospinal fluid cell count and protein levels decreased to normal levels, and hydrocephalus resolved. Moreover, other lesions including a corneal cyst also responded to vemurafenib. The brain tumor continued shrinking after 6 months of treatment. We present a genodermatosis syndrome associated with BRAF c.1799T>A p.V600E mosaicism. This syndrome may represent a new entity in the mosaic RASopathies, partly overlapping with Schimmelpenning‐Feuerstein‐Mims syndrome, which is driven by mosaicism of HRAS and/or KRAS activating mutations. Screening for BRAF c.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most‐druggable targets. © 2015 Wiley Periodicals, Inc.
Tentative clinical diagnosis of Lujan‐Fryns syndrome—A conglomeration of different genetic entities?
Authors: Hackmann Karl , Rump Andreas , Haas Stefan A. , Lemke Johannes R. , Fryns Jean‐Pierre , Tzschach Andreas , Wieczorek Dagmar , Albrecht Beate , Kuechler Alma , Ripperger Tim , Kobelt Albrecht , Oexle Konrad , Tinschert Sigrid , Schrock Evelin , Kalscheuer Vera M. , Di Donato Nataliya
Published: September 2015

The clinical diagnosis of Lujan‐Fryns syndrome (LFS) comprises X‐linked intellectual disability (XLID) with marfanoid habitus, distinct combination of minor facial anomalies and nasal speech. However the definition of syndrome was significantly broadened since the original report and implies ID with marfanoid habitus. Mutations of three genes (MED12, UPF3B, and ZDHHC9) have been reported in “broadly defined” LFS. We examined these genes in 28 individuals with a tentative clinical diagnosis of LFS but we did not identify any causative mutation. By molecular karyotyping we detected other disorders, i.e., Phelan‐McDermid syndrome and 16p11.2 microduplication, each in one patient. One affected individual was carrier of a different recurrent duplication on 16p11.2 that has been reported several times to the DECIPHER and ISCA databases in individuals with autism, intellectual disability (ID), and developmental delay. It may represent a new duplication syndrome. We also identified previously unreported de novo duplication on chromosome 12p13.31 which we considered to be disease‐causing. X‐exome sequencing of four individuals revealed private or non‐recurrent mutations in NKAP and LAS1L in one patient each. While LFS is defined as a form of XLID, there seem to be various conditions that have rather similar phenotypes. Therefore, the combination of ID and marfanoid habitus in a male patient is not sufficient for the diagnosis of LFS. We suggest that the diagnosis of LFS in patients with ID and marfanoid habitus should be made only in presence of specific facial features, nasal speech and obvious X‐linked segregation of the disorder or an unambiguously pathogenic mutation in the MED12. © 2015 Wiley Periodicals, Inc.
On the Trail of the Higgs Boson
Authors: Peskin Michael E.
Published: September 2015

I review theoretical issues associated with the Higgs boson and the mystery of spontaneous breaking of the electroweak gauge symmetry. This essay is intended as an introduction to the special issue of Annalen der Physik, “Particle Physics after the Higgs”.

image
Alkyne hydrogenation using Pd–Ag hybrid nanocatalysts in surface‐immobilized dendrimers
Authors: Karakhanov Edward A. , Maximov Anton L. , Zolotukhina Anna V. , Yatmanova Nadezhda , Rosenberg Edward
Published: September 2015

A series of Pd–Ag mixed‐metal nanocatalysts were prepared by reduction of Pd–Ag salts in the presence of poly(propylene imine) dendrimers, which were covalently bound to the surface of a silica polyamine composite, BP‐1 (polyallylamine covalently bound to a silanized amorphous silica gel). Three different Pd‐to‐Ag ratios were evaluated (50:50, catalyst 1; 40:60, catalyst 2; 60:40, catalyst 3) with the goal of determining how the amount of Ag effects selectivity, rate and conversion in the selective reduction of alkynes, such as phenylacetylene and 1‐ or 4‐octyne, to the corresponding alkenes. Conditions for the catalysis are reported where there is improved selectivity without a serious reduction in rate when compared with the analogous Pd‐only catalysts. Catalyst 2 worked best for phenylacetylene and catalyst 3 worked best for the octynes. The catalysts could be reused seven times without loss of activity. Copyright © 2015 John Wiley & Sons, Ltd.
Investigation on thermal behavior and sulfur release characteristics from rice husk and bituminous coal co‐firing under O2/CO2 atmosphere
Authors: Huang Yaji , Zhang Lihui , Duan Feng
Published: September 2015

The synergistic interaction of rice husk (RH), Huaibei bituminous coal (HB coal), and their blends was investigated under O2/CO2 combustion condition by thermogravimetric analysis. The RH was blended with HB coal in the range of 20–40 wt% to investigate the co‐combustion profile. Meanwhile, a horizontal tube furnace was used to study the sulfur release characteristics of blended fuels under O2/CO2 atmosphere. Results showed that the synergistic interaction between RH and HB coal improved the char catalytic effect and alkali metals melt‐induced effect on the decomposition of HB coal. Burnout temperature (Tb) of blended fuels decreases significantly with an increase of RH ratio and oxygen ratio, ignition temperature (Ti) decreases with increases of RH ratio, while there is a minor decrease in Ti at higher oxygen ratio. Combustion characteristic indexes of blended fuel increase with an increase of RH ratio and oxygen ratio. The SO2 peak values decrease with increases of RH ratio, and increase with an increase of oxygen ratio and temperature. However, the mean SO2 emissions and fuel‐S conversions show the inverse trend. © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.
Self‐Sustained Resistance to Suppression of CD8+ Teff Cells at the Site of Autoimmune Inflammation Can Be Reversed by Tumor Necrosis Factor and Interferon‐γ Blockade
Authors: Petrelli Alessandra , Wehrens Ellen J. , Scholman Rianne C. , Prakken Berent J. , Vastert Sebastian J. , van Wijk Femke
Published: September 2015

Objective

Resistance of Teff cells to Treg cell–mediated suppression contributes to the breakdown of peripheral tolerance in the inflamed joints of patients with juvenile idiopathic arthritis (JIA). However, unanswered questions are whether this resistant phenotype is self‐sustained and whether CD8+ and CD4+ Teff cells share the same mechanism of resistance to suppression. We undertook this study to investigate intrinsic resistance of CD8+ Teff cells to suppression and to determine how this can be targeted therapeutically.

Methods

CD8+ or CD4+ Teff cells were cultured with or without antigen‐presenting cells (APCs) in Treg cell–dependent and –independent suppression assays. Synovial fluid (SF)–derived Teff cells were crosscultured with peripheral blood (PB) Treg cells from JIA patients or healthy controls. Tumor necrosis factor (TNF) or interferon‐γ (IFNγ) blocking agents were used to restore Teff cell responsiveness to suppression.

Results

Suppression of cell proliferation and cytokine production in CD8+ Teff cells from the SF of JIA patients was severely impaired compared to that in CD8+ Teff cells from the PB of JIA patients, regardless of the presence of APCs and CD4+ Teff cells. Similar to CD4+ Teff cells, impaired suppression of CD8+ Teff cells was shown to be an intrinsic feature of this cell population. While TNF blockade restored both CD8+ and CD4+ Teff cell susceptibility to suppression, autocrine release of IFNγ selectively sustained CD8+ Teff cell resistance, which could be relieved by IFNγ blockade.

Conclusion

Unlike CD4+ Teff cells, resistance of CD8+ Teff cells to suppression at the site of autoimmune inflammation is maintained by autocrine release of IFNγ, and blockade of IFNγ restores CD8+ Teff cell responsiveness to suppression. These findings indicate a potential therapeutic value of blocking IFNγ to restore immune regulation in JIA.