bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma
Authors: Packiriswamy Nandakumar , Upreti Deepak , Zhou Yumei , Khan Rehan , Miller Amber , Diaz Rosa M. , Rooney Cliona M. , Dispenzieri Angela , Peng Kah-Whye , Russell Stephen J. 
Published: April 2020

AbstractOncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly (P < 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.
The CRL3BTBD9 E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration
Authors: Li Lihui , Zhang Wenjuan , Liu Yue , Liu Xiaojun , Cai Lili , Kang Jihui , Zhang Yunjing , Chen Wenlian , Dong Changsheng , Zhang Yanmei , Wang Mingsong , Wei Wenyi , Jia Lijun 
Published: April 2020

AbstractTumor necrosis factor alpha-induced protein 1 (TNFAIP1) modulates a plethora of important biological processes, including tumorigenesis and cancer cell migration. However, the regulatory mechanism of TNFAIP1 degradation remains largely elusive. In the present study, with a label-free quantitative proteomic approach, TNFAIP1 was identified as a novel ubiquitin target of the Cullin-RING E3 ubiquitin ligase (CRL) complex. More importantly, Cul3-ROC1 (CRL3), a subfamily of CRLs, was identified to specifically interact with TNFAIP1 and promote its polyubiquitination and degradation. Mechanistically, BTBD9, a specific adaptor component of CRL3 complex, was further defined to bind and promote the ubiquitination and degradation of TNFAIP1 in cells. As such, downregulation of BTBD9 promoted lung cancer cell migration by upregulating the expression of TNFAIP1, whereas TNFAIP1 deletion abrogated this effect. Finally, bioinformatics and clinical sample analyses revealed that BTBD9 was downregulated while TNFAIP1 was overexpressed in human lung cancer, which was associated with poor overall survival of patients. Taken together, these findings reveal a previously unrecognized mechanism by which the CRL3BTBD9 ubiquitin ligase controls TNFAIP1 degradation to regulate cancer cell migration.
Association of congenital cardiovascular malformation and neuropsychiatric phenotypes with 15q11.2 (BP1–BP2) deletion in the UK Biobank
Authors: Williams Simon G. , Nakev Apostol , Guo Hui , Frain Simon , Tenin Gennadiy , Liakhovitskaia Anna , Saha Priyanka , Priest James R. , Hentges Kathryn E. , Keavney Bernard D. 
Published: April 2020

AbstractDeletion of a non-imprinted 500kb genomic region at chromosome 15q11.2, between breakpoints 1 and 2 of the Prader–Willi/Angelman locus (BP1–BP2 deletion), has been associated in previous studies with phenotypes including congenital cardiovascular malformations (CVM). Previous studies investigating association between BP1–BP2 deletion and CVM have tended to recruit cases with rarer and more severe CVM phenotypes; the impact of CVM on relatively unselected population cohorts, anticipated to contain chiefly less severe but commoner CHD phenotypes, is relatively unexplored. More precisely defining the impact of BP1–BP2 deletion on CVM risk could be useful to guide genetic counselling, since the deletion is frequently identified in the neurodevelopmental clinic. Using the UK Biobank (UKB) cohort of ~500,000 individuals, we identified individuals with CVM and investigated the association with deletions at the BP1–BP2 locus. In addition, we assessed the association of BP1–BP2 deletions with neuropsychiatric diagnoses, cognitive function and academic achievement. Cases of CVM had an increased prevalence of the deletion compared with controls (0.64%; OR = 1.73 [95% CI 1.08–2.75]; p = 0.03), as did those with neuropsychiatric diagnoses (0.68%; OR = 1.84 [95% CI 1.23–2.75]; p = 0.004). We conclude that BP1–BP2 deletion moderately increases the risk of the generally milder, but commoner, CVM phenotypes seen in this unselected population, in addition to its previously demonstrated association in case/control studies ascertained for CVM.
Machine-learned impurity level prediction for semiconductors: the example of Cd-based chalcogenides
Authors: Mannodi-Kanakkithodi Arun , Toriyama Michael Y. , Sen Fatih G. , Davis Michael J. , Klie Robert F. , Chan Maria K. Y. 
Published: April 2020

AbstractThe ability to predict the likelihood of impurity incorporation and their electronic energy levels in semiconductors is crucial for controlling its conductivity, and thus the semiconductor’s performance in solar cells, photodiodes, and optoelectronics. The difficulty and expense of experimental and computational determination of impurity levels makes a data-driven machine learning approach appropriate. In this work, we show that a density functional theory-generated dataset of impurities in Cd-based chalcogenides CdTe, CdSe, and CdS can lead to accurate and generalizable predictive models of defect properties. By converting any semiconductor + impurity system into a set of numerical descriptors, regression models are developed for the impurity formation enthalpy and charge transition levels. These regression models can subsequently predict impurity properties in mixed anion CdX compounds (where X is a combination of Te, Se and S) fairly accurately, proving that although trained only on the end points, they are applicable to intermediate compositions. We make machine-learned predictions of the Fermi-level-dependent formation energies of hundreds of possible impurities in 5 chalcogenide compounds, and we suggest a list of impurities which can shift the equilibrium Fermi level in the semiconductor as determined by the dominant intrinsic defects. Machine learning predictions for the dominating impurities compare well with DFT predictions, revealing the power of machine-learned models in the quick screening of impurities likely to affect the optoelectronic behavior of semiconductors.
Accelerated design and characterization of non-uniform cellular materials via a machine-learning based framework
Authors: Ma Chunping , Zhang Zhiwei , Luce Benjamin , Pusateri Simon , Xie Binglin , Rafiei Mohammad H. , Hu Nan 
Published: April 2020

AbstractCellular materials, widely found in engineered and nature systems, are highly dependent on their geometric arrangement. A non-uniform arrangement could lead to a significant variation of mechanical properties while bringing challenges in material design. Here, this proof-of-concept study demonstrates a machine-learning based framework with the capability of accelerated characterization and pattern generation. Results showed that the proposed framework is capable of predicting the mechanical response curve of any given geometric pattern within the design domain under appropriate neural network architecture and parameters. Additionally, the framework is capable of generating matching geometric patterns for a targeted response through a databank constructed from our machine learning model. The accuracy of the predictions was verified with finite element simulations and the sources of errors were identified. Overall, our machine-learning based framework can boost the design efficiency of cellular materials at unit level, and open new avenues for the programmability of function at system level.
Protein structural changes on a CubeSat under rocket acceleration profile
Authors: Luna Autumn , Meisel Jacob , Hsu Kaitlin , Russi Silvia , Fernandez Daniel 
Published: April 2020

AbstractCatalyzing life-sustaining reactions, proteins are composed by 20 different amino acids that fold into a compact yet flexible three-dimensional architecture, which dictates what their function(s) might be. Determining the spatial arrangement of the atoms, the protein’s 3D structure, enables key advances in fundamental and applied research. Protein crystallization is a powerful technique to achieve this. Unlike Earth’s crystallization experiments, biomolecular crystallization in space in the absence of gravitational force is actively sought to improve crystal growth techniques. However, the effects of changing gravitational vectors on a protein solution reaching supersaturation remain largely unknown. Here, we have developed a low-cost crystallization cell within a CubeSat payload module to exploit the unique experimental conditions set aboard a sounding rocket. We designed a biaxial gimbal to house the crystallization experiments and take measurements on the protein solution in-flight with a spectrophotometry system. After flight, we used X-ray diffraction analysis to determine that flown protein has a structural rearrangement marked by loss of the protein’s water and sodium in a manner that differs from crystals grown on the ground. We finally show that our gimbal payload module design is a portable experimental setup to take laboratory research investigations into exploratory space flights.
Graphene Plasmonic Fractal Metamaterials for Broadband Photodetectors
Authors: De Nicola Francesco , Puthiya Purayil Nikhil Santh , Miŝeikis Vaidotas , Spirito Davide , Tomadin Andrea , Coletti Camilla , Polini Marco , Krahne Roman , Pellegrini Vittorio 
Published: April 2020

AbstractMetamaterials have recently established a new paradigm for enhanced light absorption in state-of-the-art photodetectors. Here, we demonstrate broadband, highly efficient, polarization-insensitive, and gate-tunable photodetection at room temperature in a novel metadevice based on gold/graphene Sierpinski carpet plasmonic fractals. We observed an unprecedented internal quantum efficiency up to 100% from the near-infrared to the visible range with an upper bound of optical detectivity of 1011 Jones and a gain up to 106, which is a fingerprint of multiple hot carriers photogenerated in graphene. Also, we show a 100-fold enhanced photodetection due to highly focused (up to a record factor of |E/E0| ≈ 20 for graphene) electromagnetic fields induced by electrically tunable multimodal plasmons, spatially localized in self-similar fashion on the metasurface. Our findings give direct insight into the physical processes governing graphene plasmonic fractal metamaterials. The proposed structure represents a promising route for the realization of a broadband, compact, and active platform for future optoelectronic devices including multiband bio/chemical and light sensors.
Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS
Authors: Agúndez José A. G. , García-Martín Elena , García-Lainez Guillermo , Miranda Miguel A. , Andreu Inmaculada 
Published: April 2020

AbstractThe human genome is constantly attacked by endogenous and exogenous agents (ultraviolet light, xenobiotics, reactive oxygen species), which can induce chemical transformations leading to DNA lesions. To combat DNA damage, cells have developed several repair mechanisms; however, if the repair is defective, DNA lesions lead to permanent mutations. Single-cell gel electrophoresis (COMET assay) is a sensitive and well-established technique for quantifying DNA damage in individual cells. Nevertheless, this tool lacks relationship with mutagenesis. Therefore, to identify errors that give rise to mutations it would be convenient to test an alternative known procedure, such as next generation sequencing (NGS). Thus, the present work aims to evaluate the photomutagenicity of neuroleptic drug chlorpromazine (CPZ), and its N-demethylated metabolites using COMET assay and to test NGS as an alternative method to assess photomutagenesis. In this context, upon exposure to UVA radiation, COMET assay reveals CPZ-photosensitized DNA damage partially repaired by cells. Conversely with this result, metabolites demethylchlorpromazine (DMCPZ) and didemethylchlorpromazine (DDMCPZ) promote extensive DNA-photodamage, hardly repaired under the same conditions. Parallel assessment of mutagenesis by NGS is consistent with these results with minor discrepancies for DDMCPZ. To our knowledge, this is the first example demonstrating the utility of NGS for evaluating drug-induced photomutagenicity.
Brain experiments imply adaptation mechanisms which outperform common AI learning algorithms
Authors: Sardi Shira , Vardi Roni , Meir Yuval , Tugendhaft Yael , Hodassman Shiri , Goldental Amir , Kanter Ido 
Published: April 2020

AbstractAttempting to imitate the brain’s functionalities, researchers have bridged between neuroscience and artificial intelligence for decades; however, experimental neuroscience has not directly advanced the field of machine learning (ML). Here, using neuronal cultures, we demonstrate that increased training frequency accelerates the neuronal adaptation processes. This mechanism was implemented on artificial neural networks, where a local learning step-size increases for coherent consecutive learning steps, and tested on a simple dataset of handwritten digits, MNIST. Based on our on-line learning results with a few handwriting examples, success rates for brain-inspired algorithms substantially outperform the commonly used ML algorithms. We speculate this emerging bridge from slow brain function to ML will promote ultrafast decision making under limited examples, which is the reality in many aspects of human activity, robotic control, and network optimization.
Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming
Authors: Solé-Boldo Llorenç , Raddatz Günter , Schütz Sabrina , Mallm Jan-Philipp , Rippe Karsten , Lonsdorf Anke S. , Rodríguez-Paredes Manuel , Lyko Frank 
Published: April 2020

AbstractFibroblasts are an essential cell population for human skin architecture and function. While fibroblast heterogeneity is well established, this phenomenon has not been analyzed systematically yet. We have used single-cell RNA sequencing to analyze the transcriptomes of more than 5,000 fibroblasts from a sun-protected area in healthy human donors. Our results define four main subpopulations that can be spatially localized and show differential secretory, mesenchymal and pro-inflammatory functional annotations. Importantly, we found that this fibroblast ‘priming’ becomes reduced with age. We also show that aging causes a substantial reduction in the predicted interactions between dermal fibroblasts and other skin cells, including undifferentiated keratinocytes at the dermal-epidermal junction. Our work thus provides evidence for a functional specialization of human dermal fibroblasts and identifies the partial loss of cellular identity as an important age-related change in the human dermis. These findings have important implications for understanding human skin aging and its associated phenotypes.
Targeted point mutations of the m6A modification in miR675 using RNA-guided base editing induce cell apoptosis
Authors: Hao Jindong , Li Chengshun , Lin Chao , Hao Yang , Yu Xianfeng , Xia Yidan , Gao Fei , Jiang Ziping , Wang Dongxu 
Published: April 2020

Abstract
Methylation of the adenine base at the nitrogen 6 position (m6A) is the most common post-transcriptional epigenetic modification of RNA, and it plays a very important role in regulating gene expression. To investigate the role of m6A methylation in the expression of non-coding RNA and miRNA, we used a system of adenine base editors (ABEs). Here, we mutated regions up- and downstream of miRNA 675 m6A modification sites in the H19 locus using HEK293T, L02, MHCC97L, MHCC97H, A549, and SGC-7901 cells. Our results showed that a T–A base transversion had occurred in all cell lines. Moreover, mutation of the regions upstream of the miRNA 675 m6A modification site led to reduced expression of H19 and the induction of cell apoptosis in HEK293T cells. To further confirm our results, L02 and MHCC97L cells were detected using ABEs system. The results indicated increased cell apoptosis and reduced expression of miR675 as well as H19. To confirm the relationship between H19 and miR675 expression, overexpression and knockdown studies were performed. The results showed that reduced HI9 expression induced cell apoptosis through miR675. Taken together, these results indicate that m6A modification can regulate the expression of H19 and miR675 which induce cell apoptosis.
Radial-velocity variations due to meridional flows in the Sun and solar-type stars: impact on exoplanet detectability
Authors: Meunier N. , Lagrange A.-M. 
Published: April 2020

Context. Stellar variability due to magnetic activity and flows at different spatial scales strongly impacts radial velocities. This variability is seen as oscillations, granulation, supergranulation, and meridional flows. The effect of this latter process is currently poorly known but could affect exoplanet detectability.
Aims. We aim to quantify the amplitude of the meridional flow integrated over the disc and its temporal variability, first for the Sun, as seen with different inclinations, and then for other solar-type stars. We then want to compare these amplitudes with low-mass exoplanetary amplitudes in radial velocity.
Methods. We used long time series (covering two 11-yr cycles) of solar latitudinal meridional circulation to reconstruct its integrated contribution and study its properties. We then used scaling laws from hydrodynamical simulations relating the amplitude of the meridional flow variability with stellar mass and rotation rate to estimate the typical amplitude expected for other solar-type stars.
Results. We find typical rms of the order of 0.5–0.7 m s−1 (edge-on) and 1.2–1.7 m s−1 (pole-on) for the Sun (peak-to-peak amplitudes are typically 1–1.4 m s−1 and 2.3–3.3 m s−1 resp.), with a minimal jitter for an inclination of 45–55°. This signal is significant compared to other stellar activity contributions and is much larger than the radial-velocity signal of the Earth. The variability is strongly related to the activity cycle, with maximum flows during the descending phase of the cycle, and possible variability on timescales lower than the cycle period. Extension to other solar-type stars shows that the variability due to meridional flows is dominated by the amplitude of the cycle of those stars (compared with mass and rotation rate), and that the peak-to-peak amplitudes can reach 4 m s−1 for the most variable stars when seen pole-on. The meridional flow contribution sometimes represents a high fraction of the convective blueshift inhibition signal, especially for quiet, low-mass stars. For fast-rotating stars, the presence of multi-cellular patterns should significantly decrease the meridional flow contribution to the radial-velocity signal.
Conclusions. Our study shows that these meridional flows could be critical for exoplanet detection. Low inclinations are more impacted than edge-on configurations, but these latter still exhibit significant variability. Meridional flows also degrade the correlation between radial velocities due to convective blueshift inhibition and chromospheric activity indicators. This will make the correction from this signal challenging for stars with no multi-cellular patterns, such as the Sun for example, although there may be some configurations for which the line shape variations may be used if the precision is sufficient.
Verhalten und Fertilität von Sauen in Gruppenhaltung
Authors: Sievert Maren 
Published: April 2020

Campler M, Pairis-Garcia M, Kieffer J et al. Sow behavior and productivity in a small stable group housing system. J Swine Health Prod 2019; 27 (2): 76–86
Aufgrund der Veränderungen der Anforderungen an die moderne Tierhaltung ordnen immer mehr Staaten der USA die Gruppenhaltung von tragenden Sauen an. Diese Studie untersuchte den Einfluss eines elektronischen Fütterungsautomaten mit „single-entry/exit“ in einer kleinen Gruppenhaltung auf das Verhalten, die Rangordnung und die Fruchtbarkeit von Sauen zum Zeitpunkt der 1. und 2. Trächtigkeit.
Einfluss einer evidenzbasierten Therapie auf die Lahmheitsprävalenz beim Schaf
Authors: Demattio Lukas 
Published: April 2020

Prosser NS, Purdy KJ, Green LE. Increase in the flock prevalence of lameness in ewes is associated with a reduction in farmers using evidence-based management of prompt treatment: A longitudinal observational study of 154 English sheep flocks 2013–2015. Prev Vet Med 2019; 173: 104801
Lahmheiten spielen in Betrieben mit kommerzieller Schafhaltung eine nicht unerhebliche wirtschaftliche Rolle. Zudem ist die Belastung für die Schafe unter dem Gesichtspunkt des Tierschutzes ein wichtiger Faktor. Die Studie untersuchte, ob Managementmaßnahmen, insbesondere eine schnell einsetzende Therapie (< 3 Tage nach Auftreten erster Symptome) die Prävalenz von Lahmheiten reduzieren können.
Empfehlungen für Sportler mit arterieller Hypertonie
Authors: Niebauer Josef 
Published: April 2020

ZusammenfassungAktuelle Richtlinien der Europäischen Gesellschaft für Kardiologie und anderen namhaften internationalen Fachgesellschaften geben regelmäßiger körperlicher Aktivität zur Vorbeugung und Behandlung von Herz-Kreislauf-Erkrankungen die höchste Evidenzklasse IA. Dies gilt auch für Sportler mit arterieller Hypertonie, wenngleich hier einige Besonderheiten zu beachten sind. Mit dem Ziel, Kollegen, die Sportler mit arterieller Hypertonie betreuen, eine evidenzbasierte Hilfestellung zu geben, wurden unter meiner Federführung in Zusammenarbeit mit Kollegen der Sektion Sportkardiologie der European Association of Preventive Cardiology der European Society of Cardiology diese Empfehlungen erstellt; sie können Open Access beim European Heart Journal heruntergeladen werden.