bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Molecular Adjuvant to Enhance Antigen-Specific CD8+ T Cell Responses
Authors: Halbroth Benedict R. , Sebastian Sarah , Poyntz Hazel C. , Bregu Migena , Cottingham Matthew G. , Hill Adrian V. S. , Spencer Alexandra J. 
Published: October 2018

AbstractDespite promising progress in malaria vaccine development, an efficacious subunit vaccine againstP.falciparumremains to be licensed and deployed. This study aimed to improve on the immunogenicity of the leading liver-stage vaccine candidate (ChAd63-MVA ME-TRAP), known to confer protection by eliciting high levels of antigen-specific CD8+T cells. We previously showed fusion of ME-TRAP to the human MHC class II invariant chain (Ii) could enhance CD8+T cell responses in non-human primates, but did not progress to clinical testing due to potential risk of auto-immunity by vaccination of humans with a self-antigen. Initial immunogenicity analyses of ME-TRAP fused to subdomains of the Ii showed that the Ii transmembrane domain alone can enhance CD8+T cell responses. Subsequently, truncated Ii sequences with low homology to human Ii were developed and shown to enhance CD8+T cell responses. By systematically mutating the TM domain sequence, multimerization of the Ii chain was shown to be important for immune enhancement. We subsequently identified several proteins from a variety of microbial pathogens with similar characteristics, that also enhance the CD8+T cell response and could therefore be used in viral vector vaccines when potent cell mediated immunity is required.
Murine transcription factor Math6 is a regulator of placenta development
Authors: Böing Marion , Brand-Saberi Beate , Napirei Markus 
Published: October 2018

AbstractThe murine basic helix-loop-helix transcription (bHLH) factor mouse atonal homolog 6 (Math6) is expressed in numerous organs and supposed to be involved in several developmental processes. However, so far neither all aspects nor the molecular mechanisms of Math6 function have been explored exhaustively. To analyze the in vivo function of Math6 in detail, we generated a constitutive knockout (KO) mouse (Math6−/−) and performed an initial histological and molecular biological investigation of its main phenotype. Pregnant Math6−/− females suffer from a disturbed early placental development leading to the death of the majority of embryos independent of the embryonic Math6 genotype. A few placentas and fetuses survive the severe uterine hemorrhagic events at late mid-gestation (E13.5) and subsequently develop regularly. However, these fetuses could not be born due to obstructions within the gravid uterus, which hinder the birth process. Characterization of the endogenous spatiotemporal Math6 expression during placenta development reveals that Math6 is essential for an ordered decidualization and an important regulator of the maternal-fetal endocrine crosstalk regulating endometrial trophoblast invasion and differentiation. The strongly disturbed vascularization observed in the maternal placenta appears as an additional consequence of the altered endocrine status and as the main cause for the general hemorrhagic crisis.
Morphological changes, nitric oxide production, and phagocytosis are triggered in vitro in microglia by bloodstream forms of Trypanosoma brucei
Authors: Figarella Katherine , Uzcategui Nestor L. , Mogk Stefan , Wild Katleen , Fallier-Becker Petra , Neher Jonas J. , Duszenko Michael 
Published: October 2018

AbstractThe flagellated parasite Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT). By a mechanism not well understood yet, trypanosomes enter the central nervous system (CNS), invade the brain parenchyma, and cause a fatal encephalopathy if is not treated. Trypanosomes are fast dividing organisms that, without any immune response, would kill the host in a short time. However, infected individuals survive either 6–12 months or more than 3 years for the acute and chronic forms, respectively. Thus, only when the brain defense collapses a lethal encephalopathy will occur. Here, we evaluated interactions between trypanosomes and microglial cells, which are the primary immune effector cells within the CNS. Using co-cultures of primary microglia and parasites, we found clear evidences of trypanosome phagocytosis by microglial cells. Microglia activation was also evident; analysis of its ultrastructure showed changes that have been reported in activated microglia undergoing oxidative stress caused by infections or degenerative diseases. Accordingly, an increase of the nitric oxide production was detected in supernatants of microglia/parasite co-cultures. Altogether, our results demonstrate that microglial cells respond to the presence of the parasite, leading to parasite’s engulfment and elimination.
Effect of the Ratio of Magnetite Particle Size to Microwave Penetration Depth on Reduction Reaction Behaviour by H2
Authors: Amini Ahmadreza , Ohno Ko-ichiro , Maeda Takayuki , Kunitomo Kazuya 
Published: October 2018

AbstractIn this study, we investigated reduction of magnetite by H2 during microwave irradiation. This process combines the advantages of microwave irradiation and using H2 as a reducing agent to mitigate CO2 emissions during the ironmaking process. Weight change measurements showed that a reduction of 75% was achieved after treatment under H2 for 60 min. For better understanding of the effective parameters in microwave chemistry, scanning electron microscopy, combined with energy-dispersive X-ray spectroscopy (SEM-EDX), was performed, which demonstrated a greater reduction of large particles (>40 μm) than small particles. This behaviour could be attributed to the higher microwave absorption capability of large particles with a higher ratio of particle size to penetration depth (d/δ). Small particles behave as transparent material and are heated via conduction and/or convection; thus, there is no contribution from the catalytic effect of microwaves to the reduction reaction. Moreover, the reduction of Fe3O4 to Fe0.94O, followed by transformation to Fe, seems to proceed from the surface toward the centre of the particle despite the volumetric microwave heating. This could be due to the higher gas accessibility of iron oxide on the particle surface than in the particle centre.
Whipping IC 63/IC 59
Authors: Andrews H. , Peeters E. , Tielens A. G. G. M. , Okada Y. 
Published: October 2018

Context. IC 63 and IC 59 are a pair of cometary-shaped nebulae in the vicinity of the star γCas (also known as Tsih, “the Whip”). Both nebulae have very different optical appearances, despite the fact that both objects lie at similar projected distances from the star: IC 63 shows bright rims and filaments, while IC 59 looks more homogeneous and faint.
Aims. We aim to perform a general description of the two nebulae from an observational standpoint in order to study the physical conditions at the UV-illuminated surfaces of these objects.
Methods. We used the available data on both nebulae taken with Spitzer and Herschel to study the infrared emission at the tip of both clouds, and derive the intensity of the UV radiation field. Using the photodetector array camera and spectrometer (PACS) in line spectroscopy mode, we obtained the intensity of the cooling lines [C II] 157 μm and [O I] 63 μm, and we used these to estimate the density in these regions. Excitation diagrams of molecular hydrogen were obtained to derive the gas temperature. We also used [C II] 157 μm velocity maps of IC 59 taken with German REceiver for Astronomy at Terahertz frequencies (GREAT) on board SOFIA to explore the gas dynamics in this nebula.
Results. We find that the IR emission from polycyclic aromatic hydrocarbons (PAHs) is very similar at the tip of both nebulae. Even though it varies in intensity between the two, the derived PAH band ratios are remarkably similar. These ratios are similar to those found in the more shielded regions of other nebulae such as NGC 7023 and NGC 2023. Regarding the physical conditions, we get that while in IC 63 the intensity of the UV field, G0, is a factor of approximately ten higher than in IC 59, the density n at the tip of IC 59 is lower than in IC 63 by a similar factor. For both objects we derive G0 values significantly lower than what previous works have so far assumed. Comparison with other reflection nebulae photo-dissociation regions (PDRs) and known correlations support our claim that both IC 63 and IC 59 are low-UV irradiated environments.
Conclusions. We conclude that the tips of IC 63 and IC 59 are about three and five times farther away from the star than their respective projected distances. The similarity of the mid-infrared emission between the two nebulae is consistent not only with both objects being overdensities within the same region around γCas, but it is also consistent with the similar G0/n and ionization parameters, which altogether rule the evolution of the hydrogenation and ionization level of the emitting population of PAHs. Finally, regarding the kinematics of the material in IC 59, we find evidence of photo-evaporation due to the incident radiation from γCas.
Sharpening up Galactic all-sky maps with complementary data
Authors: Müller Ancla , Hackstein Moritz , Greiner Maksim , Frank Philipp , Bomans Dominik J. , Dettmar Ralf-Jürgen , Enßlin Torsten 
Published: October 2018

Context. Galactic all-sky maps at very disparate frequencies, such as in the radio and γ-ray regime, show similar morphological structures. This mutual information reflects the imprint of the various physical components of the interstellar medium.
Aims. We want to use multifrequency all-sky observations to test resolution improvement and restoration of unobserved areas for maps in certain frequency ranges. For this we aim to reconstruct or predict from sets of other maps all-sky maps that, in their original form, lack a high resolution compared to other available all-sky surveys or are incomplete in their spatial coverage. Additionally, we want to investigate the commonalities and differences that the interstellar medium components exhibit over the electromagnetic spectrum.
Methods. We built an n-dimensional representation of the joint pixel-brightness distribution of n maps using a Gaussian mixture model and investigate how predictive it is. We study the extend to which one map of the training set can be reproduced based on subsets of other maps?
Results. Tests with mock data show that reconstructing the map of a certain frequency from other frequency regimes works astonishingly well, predicting reliably small-scale details well below the spatial resolution of the initially learned map. Applied to the observed multifrequency data sets of the Milky Way this technique is able to improve the resolution of, for example, the low-resolution Fermi-LAT maps as well as to recover the sky from artifact-contaminated data such as the ROSAT 0.855 keV map. The predicted maps generally show less imaging artifacts compared to the original ones. A comparison of predicted and original maps highlights surprising structures, imaging artifacts (fortunately not reproduced in the prediction), and features genuine to the respective frequency range that are not present at other frequency bands. We discuss limitations of this machine learning approach and ideas how to overcome them. In particular, with increasing sophistication of the method, such as introducing more internal degrees of freedom, it starts to internalize imaging artifacts.
Conclusions. The approach is useful to identify particularities in astronomical maps and to provide detailed educated guesses of the sky morphology at not yet observed resolutions and locations.
The XXL Survey
Authors: Pacaud F. , Pierre M. , Melin J.-B. , Adami C. , Evrard A. E. , Galli S. , Gastaldello F. , Maughan B. J. , Sereno M. , Alis S. , Altieri B. , Birkinshaw M. , Chiappetti L. , Faccioli L. , Giles P. A. , Horellou C. , Iovino A. , Koulouridis E. , Le Fèvre J.-P. , Lidman C. , Lieu M. , Maurogordato S. , Moscardini L. , Plionis M. , Poggianti B. M. , Pompei E. , Sadibekova T. , Valtchanov I. , Willis J. P. 
Published: October 2018

Context. We present an estimation of cosmological parameters with clusters of galaxies.
Aims. We constrain the Ωm, σ8, and w parameters from a stand-alone sample of X-ray clusters detected in the 50 deg2 XMM-XXL survey with a well-defined selection function.
Methods. We analyse the redshift distribution of a sample comprising 178 high signal-to-noise ratio clusters out to a redshift of unity. The cluster sample scaling relations are determined in a self-consistent manner.
Results. In a lambda cold dark matter (ΛCDM) model, the cosmology favoured by the XXL clusters compares well with results derived from the Planck Sunyaev-Zel’dovich clusters for a totally different sample (mass/redshift range, selection biases, and scaling relations). However, with this preliminary sample and current mass calibration uncertainty, we find no inconsistency with the Planck CMB cosmology. If we relax the w parameter, the Planck CMB uncertainties increase by a factor of ~10 and become comparable with those from XXL clusters. Combining the two probes allows us to put constraints on Ωm = 0.316 ± 0.060, σ8 = 0.814 ± 0.054, and w = −1.02 ± 0.20.
Conclusions. This first self-consistent cosmological analysis of a sample of serendipitous XMM clusters already provides interesting insights into the constraining power of the XXL survey. Subsequent analysis will use a larger sample extending to lower confidence detections and include additional observable information, potentially improving posterior uncertainties by roughly a factor of 3.
Causal Therapies in Mucopolysaccharidoses: Enzyme Replacement Therapy
Authors: Vartanyan Ara , Montaño Adriana 
Published: October 2018

AbstractEnzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) is the treatment of choice for patients, since it specifically addresses the underlying cause of the disease. Intravenous weekly infusions of recombinant enzymes for MPS I, II, IVA, VI, and VII have proven to be safe and efficacious for somatic symptoms. ERT has been shown to decrease urinary glycosaminoglycan levels and organomegaly, while improving stamina of patients, respiratory function, and quality of life. Although early administration of ERT optimizes outcomes, adult patients still benefit from treatment. ERT has been successfully used as combination therapy with hematopoietic stem cell transplant for patients with MPS I and MPS II, improving patient's cognitive outcomes. Although patients can receive benefit from ERT, current challenges include lack of improvement of neurological manifestations, limited effect on bone disease, development of immune response toward the infused enzyme, and high cost. We will discuss the milestones achieved by intravenous ERT for MPS diseases as well as the current challenges.
Innovative Treatments for Mucopolysaccharidoses
Authors: Lagler Florian 
Published: October 2018

AbstractMucopolysaccharidoses (MPSs) are caused by deficiency of specific lysosomal enzymes that affect the degradation of mucopolysaccharides or glycosaminoglycans. Since more than 15 years enzyme replacement therapies are available for an increasing number of MPSs. These therapies together with hematopoietic stem cell transplantation today are the gold standard of causal treatment in MPS. Despite confirmed efficacy, both do not cure these severe conditions. In this article, we discuss the limitations of established and promises of emerging therapies. The limitations of intravenous enzyme replacement and cell therapy can be summarized as immune reactions against the therapeutic molecules/cells and the failure to restore enduring and sufficient enzyme concentration in all relevant tissues. Accordingly, innovative approaches comprise small molecules and encapsulated cells that do not activate antitherapeutic immune reactions, several gene therapy approaches that aim for sustained enzyme expression, and new enzymes that penetrate blood–brain and other barriers for drug distribution. This article provides an update on the state of development of these new therapies and highlights enduring challenges.
All-Polyethylene Tibial Components in Total Knee Replacement: Early Failures
Authors: Alhifzi Zaki Suliman , Khoja Yousef Tawfik , Wood Gavin C. 
Published: October 2018

AbstractIn total primary knee replacement surgery, the use of all-polyethylene tibial (APT) components has many advantages, including no backside wear and no linear dissociation. In addition, the greater polyethylene thickness permits more conservative bone resection compared with that for metal-backed components, with a lower unit cost and similar functional results. Thus, the use of an APT in primary total knee arthroplasty remains an attractive option. This is a review of 158 patients who underwent primary knee replacement using APT components from a single manufacturer. Data collection included age, American Society of Anesthesiology physical status classification, body mass index (BMI), type of deformity, the presence of diabetes mellitus, rate of revision, and characteristics associated with early failure of the components. Average follow-up time was 40 months. The revision rate for any reason was 5.6%, and the average BMI in revision cases was 37.6. Patients with a higher BMI (≥ 37.6) were significantly more likely to require revision surgery than patients with a lower BMI (p = 0.04). In our sample, high BMI was a contributing factor for early failures in total knee replacements using an APT component. Generally, polyethylene tibial components used for primary knee replacements are safe and effective, with good outcomes and subsequent lower costs to the health care system.
Severe Troponin I Elevation and Myocardial Dysfunction in a Child with Scorpion Sting
Authors: Yildizdas Dincer , Horoz Ozden , Arslan Didar , Varan Celal , Erdem Sevcan , Yılmaz Hayri , Aslan Nagehan 
Published: October 2018

Background Scorpion sting is a common medical problem and major cause of mortality and morbidity in many countries. The symptoms of envenomation are more severe in the pediatric population. The clinical manifestations of scorpion envenomation appear by activation of sympathetic and parasympathetic nervous system. Envenomation can cause multiorgan dysfunction and death.
Case Presentation and Findings In this case report, we present a pediatric patient from Adana, Southeast Anatolia, with severe scorpion envenomation with Leiurus abdullahbayrami which is an especially dangerous species for children. Severe systolic dysfunction was detected by echocardiography. Troponin I levels elevated significantly and rapidly responded to three doses of antivenom therapy.
Conclusion Early echocardiographic examination is an important procedure for patients with scorpion envenomation. Troponin I is a significant parameter to monitor the degree of cardiac injury. Antivenom therapy is the only recommended specific therapy for children with severe scorpion envenomation due to Leiurus abdullahbayrami. Abnormal echocardiography findings may require repeated doses of scorpion antivenom.
Intergroup social influence on emotion processing in the brain
Authors: Lin Lynda C. , Qu Yang , Telzer Eva H. 
Published: October 2018

SignificancePeople’s emotions are heavily influenced by others around them. While previous studies have increased our understanding of the neuroscience of social influence in various contexts, such as music ratings and facial attraction, less is known about the neural basis of social influence on emotion processing and whether the human brain is able to track information from two different sources, such as ingroup and outgroup members. We address these two gaps in the literature by showing that the brain is able to differentially track, on a trial-by-trail basis, social influence of emotions deriving from ingroup and outgroup members. Results contribute to our understanding of the neural representations subserving everyday behaviors, such as people’s influence on others’ emotions.
Intersexual conflict over seed size is stronger in more outcrossed populations of a mixed-mating plant
Authors: Raunsgard Astrid , Opedal Øystein H. , Ekrem Runa K. , Wright Jonathan , Bolstad Geir H. , Armbruster W. Scott , Pélabon Christophe 
Published: October 2018

Significance
Intersexual conflict over maternal resource allocation to offspring can lead to the evolution of imprinted genes with parent-of-origin–specific expression. However, the precise mechanism involved in the evolution of such imprinted genes is less well understood, and few clear predictions have been presented. We resolve this issue, and, using different populations of a mixed-mating plant, we demonstrate that more outcrossed paternal populations produce larger seeds when crossed with less outcrossed maternal populations, and vice versa. This provides clear support for a “tug-of-war” mechanism operating between maternally and paternally imprinted genes. Such a mechanism can have important consequences for local adaptation in offspring size in the presence of gene flow between populations with different mating systems.
Postnatal TrkB ablation in corticolimbic interneurons induces social dominance in male mice
Authors: Tan Shawn , Xiao Yixin , Yin Henry H. , Chen Albert I. , Soong Tuck Wah , Je H. Shawn 
Published: October 2018

Significance
Our ability to reason, feel, and socialize relies on the development of a tight balance between inhibition and excitation within cortical circuits. The growth factor BDNF and its receptor TrkB are important for inhibitory neuron development and have been implicated in neuropsychiatric disorders. However, the behavioral consequences of impaired BDNF/TrkB signaling are unknown. Using a transgenic mouse line, we show that mice with deletion of BDNF/TrkB signaling from cortical inhibitory neurons exhibit social dominance and decreased inhibition within the prefrontal cortex, a key region regulating social behavior. Reversal of the network imbalance with optogenetic inhibition could rescue the behavior. Our results reveal a previously uncharacterized role of growth factor signaling within cortical interneurons for the development of social cognition.
Status of radiation damage on the European XFEL undulator systems
Authors: Wolff-Fabris F , Pflueger J , Schmidt-Foehre F , Hellberg F 
Published: October 2018

Abstract
The European XFEL GmbH is a new X-ray FEL user facility and started lasing in 2017. Three movable gap SASE Undulator Systems based on hybrid NdFeB permanent magnet technology were built. Radiation damage due to machine operation affects the magnetic properties of the segments and the quality of the SASE process. Dosimeters monitor the absorbed doses in every undulator segment and each SASE system is equipped with a diagnostic undulator (DU). We report on the profile of the absorbed doses seen in the first year of the Undulator Systems operation. Magnetic field degradation higher than 3.5% in the DU is found and associated to absorbed doses up to 4.4 kGy. An initial limit of 55 Gy for the 5-m undulator segments is recommended based on the precise K-parameter determination for beam operation.