bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning enables completely automatic tuning of a quantum device faster than human experts
Authors: Moon H. , Lennon D. T. , Kirkpatrick J. , van Esbroeck N. M. , Camenzind L. C. , Yu Liuqi , Vigneau F. , Zumbühl D. M. , Briggs G. A. D. , Osborne M. A. , Sejdinovic D. , Laird E. A. , Ares N. 
Published: August 2020

AbstractVariability is a problem for the scalability of semiconductor quantum devices. The parameter space is large, and the operating range is small. Our statistical tuning algorithm searches for specific electron transport features in gate-defined quantum dot devices with a gate voltage space of up to eight dimensions. Starting from the full range of each gate voltage, our machine learning algorithm can tune each device to optimal performance in a median time of under 70 minutes. This performance surpassed our best human benchmark (although both human and machine performance can be improved). The algorithm is approximately 180 times faster than an automated random search of the parameter space, and is suitable for different material systems and device architectures. Our results yield a quantitative measurement of device variability, from one device to another and after thermal cycling. Our machine learning algorithm can be extended to higher dimensions and other technologies.
Boundary-directed epitaxy of block copolymers
Authors: Jacobberger Robert M. , Thapar Vikram , Wu Guang-Peng , Chang Tzu-Hsuan , Saraswat Vivek , Way Austin J. , Jinkins Katherine R. , Ma Zhenqiang , Nealey Paul F. , Hur Su-Mi , Xiong Shisheng , Arnold Michael S. 
Published: August 2020

AbstractDirected self-assembly of block copolymers (BCPs) enables nanofabrication at sub-10 nm dimensions, beyond the resolution of conventional lithography. However, directing the position, orientation, and long-range lateral order of BCP domains to produce technologically-useful patterns is a challenge. Here, we present a promising approach to direct assembly using spatial boundaries between planar, low-resolution regions on a surface with different composition. Pairs of boundaries are formed at the edges of isolated stripes on a background substrate. Vertical lamellae nucleate at and are pinned by chemical contrast at each stripe/substrate boundary, align parallel to boundaries, selectively propagate from boundaries into stripe interiors (whereas horizontal lamellae form on the background), and register to wide stripes to multiply the feature density. Ordered BCP line arrays with half-pitch of 6.4 nm are demonstrated on stripes >80 nm wide. Boundary-directed epitaxy provides an attractive path towards assembling, creating, and lithographically defining materials on sub-10 nm scales.
The Rad53CHK1/CHK2-Spt21NPAT and Tel1ATM axes couple glucose tolerance to histone dosage and subtelomeric silencing
Authors: Bruhn Christopher , Ajazi Arta , Ferrari Elisa , Lanz Michael Charles , Batrin Renaud , Choudhary Ramveer , Walvekar Adhish , Laxman Sunil , Longhese Maria Pia , Fabre Emmanuelle , Smolka Marcus Bustamente , Foiani Marco 
Published: August 2020

AbstractThe DNA damage response (DDR) coordinates DNA metabolism with nuclear and non-nuclear processes. The DDR kinase Rad53CHK1/CHK2 controls histone degradation to assist DNA repair. However, Rad53 deficiency causes histone-dependent growth defects in the absence of DNA damage, pointing out unknown physiological functions of the Rad53-histone axis. Here we show that histone dosage control by Rad53 ensures metabolic homeostasis. Under physiological conditions, Rad53 regulates histone levels through inhibitory phosphorylation of the transcription factor Spt21NPAT on Ser276. Rad53-Spt21 mutants display severe glucose dependence, caused by excess histones through two separable mechanisms: dampening of acetyl-coenzyme A-dependent carbon metabolism through histone hyper-acetylation, and Sirtuin-mediated silencing of starvation-induced subtelomeric domains. We further demonstrate that repression of subtelomere silencing by physiological Tel1ATM and Rpd3HDAC activities coveys tolerance to glucose restriction. Our findings identify DDR mutations, histone imbalances and aberrant subtelomeric chromatin as interconnected causes of glucose dependence, implying that DDR kinases coordinate metabolism and epigenetic changes.
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer
Authors: Vatapalli R. , Sagar V. , Rodriguez Y. , Zhao J. C. , Unno K. , Pamarthy S. , Lysy B. , Anker J. , Han H. , Yoo Y. A. , Truica M. , Chalmers Z. R. , Giles F. , Yu J. , Chakravarti D. , Carneiro B. , Abdulkadir S. A. 
Published: August 2020

AbstractThe histone methyltransferase DOT1L methylates lysine 79 (K79) on histone H3 and is involved in Mixed Lineage Leukemia (MLL) fusion leukemogenesis; however, its role in prostate cancer (PCa) is undefined. Here we show that DOT1L is overexpressed in PCa and is associated with poor outcome. Genetic and chemical inhibition of DOT1L selectively impaired the viability of androgen receptor (AR)-positive PCa cells and organoids, including castration-resistant and enzalutamide-resistant cells. The sensitivity of AR-positive cells is due to a distal K79 methylation-marked enhancer in the MYC gene bound by AR and DOT1L not present in AR-negative cells. DOT1L inhibition leads to reduced MYC expression and upregulation of MYC-regulated E3 ubiquitin ligases HECTD4 and MYCBP2, which promote AR and MYC degradation. This leads to further repression of MYC in a negative feed forward manner. Thus DOT1L selectively regulates the tumorigenicity of AR-positive prostate cancer cells and is a promising therapeutic target for PCa.
Impact of lifestyle on cytochrome P450 monooxygenase repertoire is clearly evident in the bacterial phylum Firmicutes
Authors: Padayachee Tiara , Nzuza Nomfundo , Chen Wanping , Nelson David R. , Syed Khajamohiddin 
Published: August 2020

AbstractCytochrome P450 monooxygenases (CYPs/P450s), heme thiolate proteins, are well known for their role in organisms’ primary and secondary metabolism. Research on eukaryotes such as animals, plants, oomycetes and fungi has shown that P450s profiles in these organisms are affected by their lifestyle. However, the impact of lifestyle on P450 profiling in bacteria is scarcely reported. This study is such an example where the impact of lifestyle seems to profoundly affect the P450 profiles in the bacterial species belonging to the phylum Firmicutes. Genome-wide analysis of P450s in 972 Firmicutes species belonging to 158 genera revealed that only 229 species belonging to 37 genera have P450s; 38% of Bacilli species, followed by 14% of Clostridia and 2.7% of other Firmicutes species, have P450s. The pathogenic or commensal lifestyle influences P450 content to such an extent that species belonging to the genera Streptococcus, Listeria, Staphylococcus, Lactobacillus, Lactococcus and Leuconostoc do not have P450s, with the exception of a handful of Staphylococcus species that have a single P450. Only 18% of P450s are found to be involved in secondary metabolism and 89 P450s that function in the synthesis of specific secondary metabolites are predicted. This study is the first report on comprehensive analysis of P450s in Firmicutes.
High genetic burden of type 2 diabetes can promote the high prevalence of disease: a longitudinal cohort study in Iran
Authors: Moazzam-Jazi Maryam , Najd Hassan Bonab Leila , Zahedi Asiyeh Sadat , Daneshpour Maryam S. 
Published: August 2020

AbstractType 2 diabetes (T2D) is emerging as one of the serious public health issues in both developed and developing counties. Here, we surveyed the worldwide population differentiation in T2D-associated variants and assessed the genetic burden of the disease in an ongoing Tehran Cardio-Metabolic Genetic Study (TCGS) cohort represented the Iranian population. We found multiple SNPs that were significantly depleted or enriched in at least one of the five populations of 1,000 Genome Project (African, American, East Asian, European, and South Asian) as well as the Iranian population. Interestingly, TCF7L2, a well-known associated gene with T2D, harbors the highest number of enriched risk alleles almost in all populations except for East Asian, where this gene embraces the largest number of significantly depleted risk alleles. The polygenic risk score (PRS) of the enriched risk alleles was calculated for 1,867 diabetic and 2,855 non-diabetic participants in the TCGS cohort, interestingly demonstrating that the risk of developing T2D was almost two times higher in top PRS quintile compared with the lowest quintile after adjusting for other known risk factors.
Segregation analysis of the BRCA2 c.9227G>T variant in multiple families suggests a pathogenic role in breast and ovarian cancer predisposition
Authors: Agata Simona , Tognazzo Silvia , Alducci Elisa , Matricardi Laura , Moserle Lidia , Barana Daniela , Montagna Marco 
Published: August 2020

AbstractClassification of variants in the BRCA1 and BRCA2 genes has a major impact on the clinical management of subjects at high risk for breast and ovarian cancer. The identification of a pathogenic variant allows for early detection/prevention strategies in healthy carriers as well as targeted treatments in patients affected by BRCA-associated tumors. The BRCA2 c.9227G>T p.(Gly3076Val) variant recurs in families from Northeast Italy and is rarely reported in international databases. This variant substitutes the evolutionary invariant glycine 3076 with a valine in the DNA binding domain of the BRCA2 protein, thus suggesting a high probability of pathogenicity. We analysed clinical and genealogic data of carriers from 15 breast/ovarian cancer families in whom no other pathogenic variants were detected. The variant was shown to co-segregate with breast and ovarian cancer in the most informative families. Combined segregation data led to a likelihood ratio of 81,527:1 of pathogenicity vs. neutrality. We conclude that c.9227G>T is a BRCA2 pathogenic variant that recurs in Northeast Italy. It can now be safely used for the predictive testing of healthy family members to guide preventive surgery and/or early tumor detection strategies, as well as for PARP inhibitors treatments in patients with BRCA2-associated tumors.
Optimizing bacteriophage engineering through an accelerated evolution platform
Authors: Favor Andrew H. , Llanos Carlos D. , Youngblut Matthew D. , Bardales Jorge A. 
Published: August 2020

AbstractThe emergence of antibiotic resistance has raised serious concerns within scientific and medical communities, and has underlined the importance of developing new antimicrobial agents to combat such infections. Bacteriophages, naturally occurring bacterial viruses, have long been characterized as promising antibiotic alternatives. Although bacteriophages hold great promise as medical tools, clinical applications have been limited by certain characteristics of phage biology, with structural fragility under the high temperatures and acidic environments of therapeutic applications significantly limiting therapeutic effectiveness. This study presents and evaluates the efficacy of a new accelerated evolution platform, chemically accelerated viral evolution (CAVE), which provides an effective and robust method for the rapid enhancement of desired bacteriophage characteristics. Here, our initial use of this methodology demonstrates its ability to confer significant improvements in phage thermal stability. Analysis of the mutation patterns that arise through CAVE iterations elucidates the manner in which specific genetic modifications bring forth desired changes in functionality, thereby providing a roadmap for bacteriophage engineering.
Estimation of the number of synapses in the hippocampus and brain-wide by volume electron microscopy and genetic labeling
Authors: Santuy Andrea , Tomás-Roca Laura , Rodríguez José-Rodrigo , González-Soriano Juncal , Zhu Fei , Qiu Zhen , Grant Seth G. N. , DeFelipe Javier , Merchan-Perez Angel 
Published: August 2020

AbstractDetermining the number of synapses that are present in different brain regions is crucial to understand brain connectivity as a whole. Membrane-associated guanylate kinases (MAGUKs) are a family of scaffolding proteins that are expressed in excitatory glutamatergic synapses. We used genetic labeling of two of these proteins (PSD95 and SAP102), and Spinning Disc confocal Microscopy (SDM), to estimate the number of fluorescent puncta in the CA1 area of the hippocampus. We also used FIB-SEM, a three-dimensional electron microscopy technique, to calculate the actual numbers of synapses in the same area. We then estimated the ratio between the three-dimensional densities obtained with FIB-SEM (synapses/µm3) and the bi-dimensional densities obtained with SDM (puncta/100 µm2). Given that it is impractical to use FIB-SEM brain-wide, we used previously available SDM data from other brain regions and we applied this ratio as a conversion factor to estimate the minimum density of synapses in those regions. We found the highest densities of synapses in the isocortex, olfactory areas, hippocampal formation and cortical subplate. Low densities were found in the pallidum, hypothalamus, brainstem and cerebellum. Finally, the striatum and thalamus showed a wide range of synapse densities.
miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS
Authors: Xue Yongliang , Fan Xuefang , Yang Ruobing , Jiao Yuanyuan , Li Yang 
Published: August 2020

Abstract
Background: Cardiac fibrosis after myocardial infarction (MI) is a major cause of heart deterioration. Recently, the roles of microRNAs (miRNAs) in various cardiovascular diseases associated with cardiac fibrosis have been extensively investigated. The present study aimed to investigate the role and mechanism of miR-29b-3p in cardiac fibrosis after MI.
Methods: miR-29b-3p expression in TGF-β1-activated cardiac fibroblasts (CFs) was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) and Trans-well assays were performed to evaluate CFs proliferation and migration ability, respectively. Protein expressions of α-SMA, collagen I, collagen III, MMP2, and MMP9 were examined by Western blot assay. Bioinformatics, luciferase, and RNA immunoprecipitation (RIP) assays were carried out to determine whether FOS was targeted by miR-29b-3p.
Results: TGF-β1 treatment dose-dependently curbed miR-29b-3p expression in CFs. miR-29b-3p restrained the promotive impacts of TGF-β1 on CFs proliferation, migration, and differentiation. FOS was affirmed to be a target of miR-29b-3p, elevated expression of FOS reversed the inhibitory effects of miR-29b-3p on cell proliferation, migration, and differentiation in TGF-β1-activated CFs.
Conclusion: miR-29b-3p degraded the pro-fibrosis effect induced by TGF-β1 via targeting FOS, providing a prospective therapeutic avenue for cardiac fibrosis after MI.
Perceptual and Electrophysiological Correlates of Fixed Versus Moving Sound Source Lateralization
Authors: St. George Barrett Victor , Cone Barbara 
Published: August 2020

Purpose
The aims of the study were (a) to evaluate the effects of systematically varied factors of stimulus duration, interaural-level difference (ILD), and direction on perceptual and electrophysiological metrics of lateralization for fixed versus moving targets and (b) to evaluate the hemispheric activity underlying perception of fixed versus moving auditory targets.

Method
Twelve normal-hearing, young adult listeners were evaluated using perceptual and P300 tests of lateralization. Both perceptual and P300 tests utilized stimuli that varied for type (fixed and moving), direction (right and left), duration (100 and 500 ms), and magnitude of ILD (9 and 18 dB). Listeners provided laterality judgments and stimulus-type discrimination (fixed vs. moving) judgments for all combinations of acoustic factors. During P300 recordings, listeners discriminated between left- versus right-directed targets, as the other acoustic parameters were varied.

Results
ILD magnitude and stimulus type had statistically significant effects on laterality ratings, with larger magnitude ILDs and fixed type resulting in greater lateralization. Discriminability between fixed versus moving targets was dependent on stimulus duration and ILD magnitude. ILD magnitude was a significant predictor of P300 amplitude. There was a statistically significant inverse relationship between the perceived velocity of targets and P300 latency. Lateralized targets evoked contralateral hemispheric P300 activity. Moreover, a right-hemisphere enhancement was observed for fixed-type lateralized deviant stimuli.

Conclusions
Perceptual and P300 findings indicate that lateralization of auditory movement is highly dependent on temporal integration. Both the behavioral and physiological findings of this study suggest that moving auditory targets with ecologically valid velocities are processed by the central auditory nervous system within a window of temporal integration that is greater than that for fixed auditory targets. Furthermore, these findings lend support for a left hemispatial perceptual bias and right hemispheric dominance for spatial listening.
Deciphering the Lyman α blob 1 with deep MUSE observations
Authors: Herenz Edmund Christian , Hayes Matthew , Scarlata Claudia 
Published: August 2020

Context. Lyman α blobs (LABs) are large-scale radio-quiet Lyman α (Lyα) nebula at high-z that occur predominantly in overdense proto-cluster regions. In particular, there is the prototypical SSA22a-LAB1 at z = 3.1, which has become an observational reference for LABs across the electromagnetic spectrum.
Aims. We want to understand the powering mechanisms that drive the LAB so that we may gain empirical insights into the galaxy-formation processes within a rare dense environment at high-z. Thus, we need to infer the distribution, the dynamics, and the ionisation state of LAB 1’s Lyα emitting gas.
Methods. LAB 1 was observed for 17.2 h with the VLT/MUSE integral-field spectrograph. We produced optimally extracted narrow band images, in Lyαλ1216, He IIλ1640, and we tried to detect C IVλ1549 emission. By utilising a moment-based analysis, we mapped the kinematics and the line profile characteristics of the blob. We also linked the inferences from the line profile analysis to previous results from imaging polarimetry.
Results. We map Lyα emission from the blob down to surface-brightness limits of ≈6 × 10−19 erg s−1 cm−2 arcsec−2. At this depth, we reveal a bridge between LAB 1 and its northern neighbour LAB 8, as well as a shell-like filament towards the south of LAB 1. The complexity and morphology of the Lyα profile vary strongly throughout the blob. Despite the complexity, we find a coherent large-scale east-west velocity gradient of ∼1000 km s−1 that is aligned perpendicular to the major axis of the blob. Moreover, we observe a negative correlation of Lyα polarisation fraction with Lyα line width and a positive correlation with absolute line-of-sight velocity. Finally, we reveal He II emission in three distinct regions within the blob, however, we can only provide upper limits for C IV.
Conclusions. Various gas excitation mechanisms are at play in LAB 1: ionising radiation and feedback effects dominate near the embedded galaxies, while Lyα scattering contributes at larger distances. However, He II/Lyα ratios combined with upper limits on C IV/Lyα are not able to discriminate between active galactic nucleus ionisation and feedback- driven shocks. The alignment of the angular momentum vector parallel to the morphological principal axis appears to be at odds with the predicted norm for high-mass halos, but this most likely reflects that LAB 1 resides at a node of multiple intersecting filaments of the cosmic web. LAB 1 can thus be thought of as a progenitor of a present-day massive elliptical within a galaxy cluster.
Interferometric study on the temporal variability of the brightness distributions of protoplanetary disks
Authors: Kobus J. , Wolf S. , Ratzka T. , Brunngräber R. 
Published: August 2020

Context. Optical and infrared spatially unresolved multi-epoch observations have revealed the variability of pre-main sequence stars and/or their environment. Moreover, structures in orbital motion around the central star, resulting from planet-disk interaction, are predicted to cause temporal variations in the brightness distributions of protoplanetary disks. Through repeated observations of pre-main sequence stars with the Very Large Telescope Interferometer (VLTI) over nearly two decades, the ESO Archive has become a treasure chest containing unprecedented high-resolution multi-epoch near- and mid-infrared observations of the potential planet-forming regions in protoplanetary disks.
Aims. We aim to investigate whether the existing multi-epoch observations provide evidence for the variability of the brightness distributions of the innermost few astronomical units of protoplanetary disks and to quantify any variations detected.
Methods. We present different approaches to search for evidence of temporal variations based on multi-epoch observations obtained with the VLTI instruments PIONIER, AMBER, and MIDI for 68 pre-main sequence stars.
Results. For nine objects in our sample, multi-epoch data obtained using equal baselines are available that allow us to directly detect variations in the visibilities due to temporally variable brightness distributions. Significant variations of the near-infrared visibilities obtained in different epochs with PIONIER and/or AMBER for HD 50138, DX Cha, HD 142527, V856 Sco, HD 163296, and R CrA were found. HD 37806, TW Hya, and CPD-36 6759 show no significant variations. By estimating the impact of a small variation of the baseline on the measured squared visibilities, we are able to compare the data of another 12 pre-main sequence stars. Thereby, we find evidence for temporal variations of the brightness distribution of one additional object, AK Sco. Besides the two binaries DX Cha and AK Sco, HD 50138 and V856 Sco also show signs of variability caused by variations of asymmetric structures in the brightness distribution.
Preliminary Results of Extracorporeal Membrane Oxygenation Assisted Tracheal Sleeve Pneumonectomy for Cancer
Authors: Spaggiari Lorenzo , Sedda Giulia , Petrella Francesco , Venturino Marco , Rossi Fabiana , Guarize Juliana , Galetta Domenico , Casiraghi Monica , Iacono Giorgio Lo , Bertolaccini Luca , Alamanni Francesco 
Published: August 2020

Abstract
Objective Tracheal sleeve pneumonectomy is a challenge in lung cancer management and in achieving long-term oncological results. In November 2018, we started a prospective study on the role of extracorporeal membrane oxygenation (ECMO) in tracheal sleeve pneumonectomy. We aim to present our preliminary results.
Methods From November 2018 to November 2019, six patients (three men and three women; median age: 61 years) were eligible for tracheal sleeve pneumonectomy for lung cancer employing the veno-venous ECMO during tracheobronchial anastomosis.
Results Only in one patient, an intrapericardial pneumonectomy without ECMO support was performed, but cannulas were maintained during surgery. The median length of surgery was 201 minutes (range: 162–292 minutes), and the average duration of the apneic phase was 38 minutes (range: 31–45 minutes). No complications correlated to the positioning of the cannulas were recorded. There was only one major postoperative complication (hemothorax). At the time of follow-up, all patients were alive; one patient alive with bone metastasis was being treated with radiotherapy.
Conclusion ECMO-assisted oncological surgery was rarely described, and its advantages include hemodynamic stability with low bleeding complications and a clean operating field. As suggested by our preliminary data, ECMO-assisted could be a useful alternative strategy in select lung cancer patients.