bluuebunny/crossref_metadata_2025 huggingface dataset:
STABLY MEASURABLE CARDINALS
Authors: WELCH PHILIP D.
Published: June 2020

We define a weak iterability notion that is sufficient for a number of arguments concerning
$\Sigma _{1}$
-definability at uncountable regular cardinals. In particular we give its exact consistency strength first in terms of the second uniform indiscernible for bounded subsets of
$\kappa $
:
$u_2(\kappa )$
, and secondly to give the consistency strength of a property of Lücke’s.

TheoremThe following are equiconsistent:

(i)

There exists
$\kappa $
which is stably measurable;

(ii)

for some cardinal
$\kappa $
,
$u_2(\kappa )=\sigma (\kappa )$
;

(iii)

The
$\boldsymbol {\Sigma }_{1}$
-club property holds at a cardinal
$\kappa $
.

Here
$\sigma (\kappa )$
is the height of the smallest
$M \prec _{\Sigma _{1}} H ( \kappa ^{+} )$
containing
$\kappa +1$
and all of
$H ( \kappa )$
. Let
$\Phi (\kappa )$
be the assertion:

TheoremAssume
$\kappa $
is stably measurable. Then
$\Phi (\kappa )$
.

And a form of converse:

TheoremSuppose there is no sharp for an inner model with a strong cardinal. Then in the core model K we have:
$\mbox {``}\exists \kappa \Phi (\kappa ) \mbox {''}$
is (set)-generically absolute
${\,\longleftrightarrow \,}$
There are arbitrarily large stably measurable cardinals.

When
$u_2(\kappa ) < \sigma (\kappa )$
we give some results on inner model reflection.
Composition and consequences of the IntCal20 radiocarbon calibration curve
Authors: Reimer Paula J.
Published: June 2020

Radiocarbon calibration is necessary to correct for variations in atmospheric radiocarbon over time. The IntCal working group has developed an updated and extended radiocarbon calibration curve, IntCal20, for Northern Hemisphere terrestrial samples from 0 to 55,000 cal yr BP. This paper summarizes the new datasets, changes to existing datasets, and the statistical method used for constructing the new curve. Examples of the effect of the new calibration curve compared to IntCal13 for hypothetical radiocarbon ages are given. For the recent Holocene the effect is minimal, but for older radiocarbon ages the shift in calibrated ages can be up to several hundred years with the potential for multiple calibrated age ranges in periods with higher-resolution data. In addition, the IntCal20 curve is used to recalibrate the radiocarbon ages for the glaciation of the Puget Lowland and to recalculate the advance rate. The ice may have reached its maximum position a few hundred years earlier using the new calibration curve; the calculated advance rate is virtually unchanged from the prior estimate.
UK Internet antenatal dietary advice: a content accuracy and readability analysis
Authors: Sidnell Anne , Nestel Penelope
Published: June 2020

The aim of the study was to assess the accuracy and readability of Internet prenatal nutrition advice. Between August and December 2018, 130 Internet pages returned from Google searches on foods to avoid, foods to eat and supplements use were compared with UK government advice for pregnant women. Readability was assessed using the Flesch Readability Ease (FRE) tool. Descriptive and non-parametric tests were used. Spearman’s correlation explored associations between accuracy and readability. Kruskal–Wallis tests with Bonferroni correction were used for multiple pairwise tests and Mann–Whitney U tests for two-sample differences in medians. A total of 130 Internet pages were examined: 48 % from publishers, 27 % from other commercial organisations, 22 % from charities and 3 % from governments. Eighty-three (64 %) pages contained inaccurate and accurate advice, twenty-three (18 %) were accurate and complete, twenty-one (16 %) were inaccurate, and three (2 %) lacked any relevant advice. The median percentage accuracy of all advice was 83 (lower quartile, upper quartile: 48, 100). Median FRE was 55 (46, 61) ‘fairly difficult’. Eighty-seven pages (67 %) scored below the recommended FRE for public Internet pages. There was a weak positive correlation between accuracy and readability of Internet pages (rho = 0·241, P = 0·006). Accuracy of Internet pages did not differ by dietary theme. Pages on supplements were the most difficult to read. Internet pages from publishers and other commercial organisations were significantly less accurate than those from not-for-profit organisations (median percentage difference –8 (–29, 0·00), P = 0·019). Much pregnancy-related dietary advice online is inaccurate and difficult to read. Advice should be developed in consultation with qualified nutritionists and dietitians.
Using environmental niche modelling to investigate abiotic predictors of crocodilian attacks on people
Authors: Powell George , Versluys Thomas M. M. , Williams Jessica J. , Tiedt Sonia , Pooley Simon
Published: June 2020

Crocodilians are distributed widely through the tropics and subtropics, and several species pose a substantial threat to human life. This has important implications for human safety and crocodilian conservation. Understanding the drivers of crocodilian attacks on people could help minimize future attacks and inform conflict management. Crocodilian attacks follow a seasonal pattern in many regions, but there has been limited analysis of the relationship between attack occurrence and fine-scale contemporaneous environmental conditions. We use methods from environmental niche modelling to explore the relationships between attacks on people and abiotic predictors at a daily temporal resolution for the Nile crocodile Crocodylus niloticus in South Africa and Eswatini (formerly Swaziland), and the American alligator Alligator mississippiensis in Florida, USA. Our results indicate that ambient daily temperature is the most important abiotic temporal predictor of attack occurrence for both species, with attack likelihood increasing markedly when mean daily temperatures exceed 18 °C and peaking at 28 °C. It is likely that this relationship is explained partially by human propensity to spend time in and around water in warmer weather but also by the effect of temperature on crocodilian hunting behaviour and physiology, especially the ability to digest food. We discuss the potential of our findings to contribute to the management of crocodilians, with benefits for both human safety and conservation, and the application of environmental niche modelling for understanding human–wildlife conflicts involving both ectotherms and endotherms.
Challenging the negative learning bias hypothesis of depression: reversal learning in a naturalistic psychiatric sample
Authors: Brolsma Sophie C. A. , Vrijsen Janna N. , Vassena Eliana , Rostami Kandroodi Mojtaba , Bergman M. Annemiek , van Eijndhoven Philip F. , Collard Rose M. , den Ouden Hanneke E. M. , Schene Aart H. , Cools Roshan
Published: June 2020

Background

Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample.

Methods

We administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling.

Results

In contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias.

Conclusions

These results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.
INFERENCE IN DYNAMIC, NONPARAMETRIC MODELS OF PRODUCTION: CENTRAL LIMIT THEOREMS FOR MALMQUIST INDICES
Authors: Kneip Alois , Simar Léopold , Wilson Paul W.
Published: June 2020

The Malmquist index gives a measure of productivity in dynamic settings and has been widely applied in empirical work. The index is typically estimated using envelopment estimators, particularly data envelopment analysis (DEA) estimators. Until now, inference about productivity change measured by Malmquist indices has been problematic, including both inference regarding productivity change experienced by particular firms as well as mean productivity change. This paper establishes properties of a DEA-type estimator of distance to the conical hull of a variable returns to scale production frontier. In addition, properties of DEA estimators of Malmquist indices for individual producers are derived as well as properties of geometric means of these estimators. The latter requires new central limit theorem results, extending the work of Kneip, Simar, and Wilson (2015, Econometric Theory 31, 394–422). Simulation results are provided to give applied researchers an idea of how well inference may work in practice in finite samples. Our results extend easily to other productivity indices, including the Luenberger and Hicks–Moorsteen indices.
Impact of New GPS Signals on Positioning Accuracy for Urban Bus Operations
Authors: Elhajj Mireille , Ochieng Washington
Published: June 2020

This paper analyses for the first time the impact of new GPS signals on positioning accuracy for dynamic urban applications, taking bus operations as an example. The performance assessment addresses both code measurement precision and positioning accuracy. The former is based on signal-to-noise ratio and estimation of multipath and noise by a combination of code and carrier phase measurements. The impact on positioning accuracy is derived by comparing the performance achievable with the conventional single frequency GPS only positioning both relative to reference trajectories from the integration of carrier phase measurements with data from a high grade inertial measurement unit. The results show that L5 code measurements have the highest precision, followed by L1 C/A and L2C. In the positioning domain, there is a significant improvement in two-dimensional and three-dimensional accuracy from dual frequency code measurements over the single frequency measurements, of 39% and 48% respectively, enabling more bus operation services to be supported.
Approximate solutions to one-phase Stefan-like problems with space-dependent latent heat
Authors: BOLLATI J. , TARZIA D. A.
Published: June 2020

The work in this paper concerns the study of different approximations for one-dimensional one-phase Stefan-like problems with a space-dependent latent heat. It is considered two different problems, which differ from each other in their boundary condition imposed at the fixed face: Dirichlet and Robin conditions. The approximate solutions are obtained by applying the heat balance integral method (HBIM), the modified HBIM and the refined integral method (RIM). Taking advantage of the exact analytical solutions, we compare and test the accuracy of the approximate solutions. The analysis is carried out using the dimensionless generalised Stefan number (Ste) and Biot number (Bi). It is also studied the case when Bi goes to infinity in the problem with a convective condition, recovering the approximate solutions when a temperature condition is imposed at the fixed face. Some numerical simulations are provided in order to assert which of the approximate integral methods turns out to be optimal. Moreover, we pose an approximate technique based on minimising the least-squares error, obtaining also approximate solutions for the classical Stefan problem.
‘Turning’ everywhere in IR: on the sociological underpinnings of the field's proliferating turns
Authors: Baele Stephane J. , Bettiza Gregorio
Published: June 2020

In the past two decades, calls for International Relations (IR) to ‘turn’ have multiplied. Having reflected on Philosophy's own linguistic turn in the 1980s and 1990s, IR appears today in the midst of taking – almost simultaneously – a range of different turns, from the aesthetic to the affective, from the historical to the practice, from the new material to the queer. This paper seeks to make sense of this puzzling development. Building on Bourdieu's sociology of science, we argue that although the turns ostensibly bring about (or resuscitate) ambitious philosophical, ontological, and epistemological questions to challenge what is deemed to constitute the ‘mainstream’ of IR, their impact is more likely to be felt at the ‘margins’ of the discipline. From this perspective, claiming a turn constitutes a position-enhancing move for scholars seeking to accumulate social capital, understood as scientific authority, and become ‘established heretics’ within the intellectual subfield of critical IR. We therefore expect the proliferation of turns to reshape more substantively what it means to do critical IR, rather than turning the whole discipline on its head.
Depth‐Dependent Azimuthal Anisotropy Beneath the Juan de Fuca Plate System
Authors: Eilon Zachary C. , Forsyth Donald W.
Published: June 2020

We use surface wave measurements to reveal anisotropy as a function of depth within the Juan de Fuca and Gorda plate system. Using a two‐plane wave method, we measure phase velocity and azimuthal anisotropy of fundamental mode Rayleigh waves, solving for anisotropic shear velocity. These surface wave measurements are jointly inverted with constraints from SKS splitting studies using a Markov chain approach. We show that the two data sets are consistent and present inversions that offer new constraints on the vertical distribution of strain beneath the plates and the processes at spreading centers. Anisotropy of the Juan de Fuca plate interior is strongest (~2.4%) in the low‐velocity zone between ~40‐ to 90‐km depth, with ENE direction driven by relative shear between plate motion and mantle return flow from the Cascadia subduction zone. In disagreement with Pn measurements, weak (~1.1%) lithospheric anisotropy in Juan de Fuca is highly oblique to the expected ridge‐perpendicular direction, perhaps connoting complex intralithospheric fabrics associated with melt or off‐axis downwelling. In the Gorda microplate, strong shallow anisotropy (~1.9%) is consistent with Pn inversions and aligned with spreading and may be enhanced by edge‐driven internal strain. Weak anisotropy with ambiguous orientation in the low‐velocity zone can be explained by Gorda's youth and modest motion relative to the Pacific. Deeper (≥90 km) fabric appears controlled by regional flow fields modulated by the Farallon slab edge: anisotropy is strong (~1.8%) beneath Gorda, but absent beneath the Juan de Fuca, which is in the strain shadow of the slab.
Variational Phase‐Field Modeling of Hydraulic Fracture Interaction With Natural Fractures and Application to Enhanced Geothermal Systems
Authors: Lepillier Baptiste , Yoshioka Keita , Parisio Francesco , Bakker Richard , Bruhn David
Published: June 2020

In every tight formation reservoir, natural fractures play an important role for mass and energy transport and stress distribution. Enhanced Geothermal Systems (EGS) make no exception, and stimulation aims at increasing the reservoir permeability to enhance fluid circulation and heat transport. EGS development relies upon the complex task of predicting accurate hydraulic fracture propagation pathway by taking into account reservoir heterogeneities and natural or preexisting fractures. In this contribution, we employ the variational phase‐field method, which handles hydraulic fracture initiation, propagation, and interaction with natural fractures and is tested under varying conditions of rock mechanical properties and natural fractures distributions. We run bidimensional finite element simulations employing the open‐source software OpenGeoSys and apply the model to simulate realistic stimulation scenarios, each one built from field data and considering complex natural fracture geometries in the order of a thousand of fractures. Key mechanical properties are derived from laboratory measurements on samples obtained in the field. Simulations results confirm the fundamental role played by natural fractures in stimulation's predictions, which is essential for developing successful EGS projects.
Optoelectronic parametric oscillator
Authors: Hao Tengfei , Cen Qizhuang , Guan Shanhong , Li Wei , Dai Yitang , Zhu Ninghua , Li Ming
Published: June 2020

Oscillators are one of the key elements in various applications as a signal source to generate periodic oscillations. Among them, an optical parametric oscillator (OPO) is a driven harmonic oscillator based on parametric frequency conversion in an optical cavity, which has been widely investigated as a coherent light source with an extremely wide wavelength tuning range. However, steady oscillation in an OPO is confined by the cavity delay, which leads to difficulty in frequency tuning, and the frequency tuning is discrete with the minimum tuning step determined by the cavity delay. Here, we propose and demonstrate a counterpart of an OPO in the optoelectronic domain, i.e., an optoelectronic parametric oscillator (OEPO) based on parametric frequency conversion in an optoelectronic cavity to generate microwave signals. Owing to the unique energy-transition process in the optoelectronic cavity, the phase evolution in the OEPO is not linear, leading to steady single-mode oscillation or multimode oscillation that is not bounded by the cavity delay. Furthermore, the multimode oscillation in the OEPO is stable and easy to realize owing to the phase control of the parametric frequency-conversion process in the optoelectronic cavity, while stable multimode oscillation is difficult to achieve in conventional oscillators such as an optoelectronic oscillator (OEO) or an OPO due to the mode-hopping and mode-competition effect. The proposed OEPO has great potential in applications such as microwave signal generation, oscillator-based computation, and radio-frequency phase-stable transfer.
USP42 enhances homologous recombination repair by promoting R-loop resolution with a DNA–RNA helicase DHX9
Authors: Matsui Misaki , Sakasai Ryo , Abe Masako , Kimura Yusuke , Kajita Shoki , Torii Wakana , Katsuki Yoko , Ishiai Masamichi , Iwabuchi Kuniyoshi , Takata Minoru , Nishi Ryotaro
Published: June 2020

The nucleus of mammalian cells is compartmentalized by nuclear bodies such as nuclear speckles, however, involvement of nuclear bodies, especially nuclear speckles, in DNA repair has not been actively investigated. Here, our focused screen for nuclear speckle factors involved in homologous recombination (HR), which is a faithful DNA double-strand break (DSB) repair mechanism, identified transcription-related nuclear speckle factors as potential HR regulators. Among the top hits, we provide evidence showing that USP42, which is a hitherto unidentified nuclear speckles protein, promotes HR by facilitating BRCA1 recruitment to DSB sites and DNA-end resection. We further showed that USP42 localization to nuclear speckles is required for efficient HR. Furthermore, we established that USP42 interacts with DHX9, which possesses DNA–RNA helicase activity, and is required for efficient resolution of DSB-induced R-loop. In conclusion, our data propose a model in which USP42 facilitates BRCA1 loading to DSB sites, resolution of DSB-induced R-loop and preferential DSB repair by HR, indicating the importance of nuclear speckle-mediated regulation of DSB repair.
Snail promotes the generation of vascular endothelium by breast cancer cells
Authors: Chang Zhenyu , Zhang Yanan , Liu Jie , Zheng Yiqiong , Li Huayue , Kong Yanjun , Li Pengyun , Peng Haiwen , Shi Yajiao , Cao Bo , Ran Fang , Chen Yingjie , Song Yuhua , Ye Qinong , Ding Lihua
Published: June 2020

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial–mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.
Intestinal vitamin D receptor knockout protects from oxazolone-induced colitis
Authors: Shi Yongyan , Liu Ziyun , Cui Xuewei , Zhao Qun , Liu Tianjing
Published: June 2020

Crohn’s disease (CD) and ulcerative colitis (UC) actually had different pathological mechanisms, as the former was mainly induced by Th1 and Th17 response and the latter by Th2 response. Our previous study found that oxazolone-induced Th2-mediated colitis could not be attenuated by vitamin D supplementation. This study investigated the influence of intestinal vitamin D receptor (VDR) knockout on oxazolone-induced colitis and explored the possible immunological mechanism. Intestinal VDR knockout mice had milder oxazolone-induced colitis than wildtype controls, as demonstrated by less body weight decrease and faster recovery, more intact local structure, reduced cell apoptosis, and better preserved barrier function. Th2-mediated inflammation was significantly inhibited by VDR deficiency. Meanwhile, the percentage of invariant natural killer T (iNKT) cells did not increase as much in intestinal VDR knockout mice as in wild-type controls, nor did the iNKT cells develop normally as in the controls. Intestinal VDR knockout protected against oxazolone-induced colitis in mice by blocking Th2 cell response and reducing the function of intestinal iNKT cells. Vitamin D status had no influence on the severity of colitis. This study may explain the diverse outcomes after vitamin D supplementation in literature and add some clue to the targeted therapy of IBD.
Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?
Authors: Lin Lihui , Zhou Gaoshi , Chen Peng , Wang Ying , Han Jing , Chen Minhu , He Yao , Zhang Shenghong
Published: June 2020

Inflammatory bowel disease (IBD), a chronic relapsing gastrointestinal inflammatory disease, mainly comprises ulcerative colitis (UC) and Crohn’s disease (CD). Although the mechanisms and pathways of IBD have been widely examined in recent decades, its exact pathogenesis remains unclear. Studies have focused on the discovery of new therapeutic targets and application of precision medicine. Recently, a strong connection between IBD and noncoding RNAs (ncRNAs) has been reported. ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). The contributions of lncRNAs and circRNAs in IBD are less well-studied compared with those of miRNAs. However, lncRNAs and circRNAs are likely to drive personalized therapy for IBD. They will enable accurate diagnosis, prognosis, and prediction of therapeutic responses and promote IBD therapy. Herein, we briefly describe the molecular functions of lncRNAs and circRNAs and provide an overview of the current knowledge of the altered expression profiles of lncRNAs and circRNAs in patients with IBD. Further, we discuss how these RNAs are involved in the nosogenesis of IBD and are emerging as biomarkers.
Mitochondrial dysfunction generates aggregates that resist lysosomal degradation in human breast cancer cells
Authors: Biel Thomas G. , Aryal Baikuntha , Gerber Michael H. , Trevino Josè G. , Mizuno Naoko , Rao V. Ashutosh
Published: June 2020

Disrupting functional protein homeostasis is an established therapeutic strategy for certain tumors. Ongoing studies are evaluating autophagy inhibition for overcoming chemotherapeutic resistance to such therapies by neutralizing lysosomal pH. New and sensitive methods to monitor autophagy in patients are needed to improve trial design and interpretation. We report that mitochondrial-damaged breast cancer cells and rat breast tumors accumulate p53-positive protein aggregates that resist lysosomal degradation. These aggregates were localized to enzymatically-active autolysosomes that were degrading autophagosomes and the autophagic receptor proteins TAX1BP1 and NDP52. NDP52 was identified to associate with aggregated proteins and knocking down NDP52 led to the accumulation of protein aggregates. TAX1BP1 was identified to partly localize with aggregates, and knocking down TAX1BP1 enhanced aggregate formation, suppressed autophagy, impaired NDP52 autophagic degradation and induced cell death. We propose that quantifying aggregates and autophagic receptors are two potential methods to evaluate autophagy and lysosomal degradation, as confirmed using primary human tumor samples. Collectively, this report establishes protein aggregates and autophagy receptors, TAX1BP1 and NDP52, as potential endpoints for monitoring autophagy during drug development and clinical studies.
microRNA-181c-5p promotes the formation of insulin-producing cells from human induced pluripotent stem cells by targeting smad7 and TGIF2
Authors: Li Ning , Jiang Doukou , He Qian , He Fei , Li Yang , Deng Chunyan , Li Furong
Published: June 2020

Generating insulin-producing cells (IPCs) from human pluripotent stem cells is a promising method for studying the molecular mechanism underlying pancreas development and a potential treatment source for type 1 diabetes. Previous studies have shown that miR-181c-5p is highly enriched in adult islets; however, its role in pancreatic β cell differentiation is poorly understood. In this study, we differentiated human induced pluripotent stem cells (hiPSCs) into IPCs in a stepwise process that recapitulated pancreas organogenesis and observed that miR-181c-5p continuously accumulated throughout the entire differentiation process. hiPSCs were transduced with lentiviral vectors containing human miR-181c-5p precursor, which significantly increased the endodermal markers SOX17, FOXA2, CXCR4 and GATA4 and pancreatic endocrine-specific gene expression, including PDX1, NKX6.1, MAFA and Insulin. miR-181c-5p overexpression exerted little effect on the efficiency of definitive endoderm, whereas it promoted the differentiation of pancreatic progenitors and IPCs, especially for NKX6.1-positive and insulin-positive cells differentiation. Transplanted these cells exhibit glucose-stimulated C-peptide secretion in vivo and protect mice from chemically induced diabetes. It was found that miR-181c-5p directly targets the 3′UTR of smad7 and TGIF2 mRNA, which are known to be endogenous repressors of TGF-β-smad2/3 signaling, to decrease their mRNA and protein levels. Furthermore, overexpressed miR-181c-5p led to an elevation of the smad2/3 phosphorylation levels in hiPSC-derived cells, while treatment with smad2/3 inhibitors following miR-181c-5p overexpression had opposite effects on IPC formation. These results suggest that miR-181c-5p is critically involved in pancreatic lineage commitment through direct repression of smad7 and TGIF2 and that it modulates TGF-β-smad2/3 signaling activation and increases the feasibility of using patient-specific hiPSCs for β cell replacement therapy for type 1 diabetes.
The pericyte connectome: spatial precision of neurovascular coupling is driven by selective connectivity maps of pericytes and endothelial cells and is disrupted in diabetes
Authors: Kovacs-Oller Tamas , Ivanova Elena , Bianchimano Paola , Sagdullaev Botir T.
Published: June 2020

Functional hyperemia, or the matching of blood flow with activity, directs oxygen and nutrients to regionally firing neurons. The mechanisms responsible for this spatial accuracy remain unclear but are critical for brain function and establish the diagnostic resolution of BOLD-fMRI. Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then tested whether this net of pericytes and surrounding neuroglia predicted a connectivity map in response to sensory stimuli. Surprisingly, we found that these connections were not only selective across cell types, but also highly asymmetric spatially. First, pericytes connected predominantly to other neighboring pericytes and endothelial cells, and less to arteriolar smooth muscle cells, and not to surrounding neurons or glia. Second, focal, but not global stimulation evoked a directional vasomotor response by strengthening connections along the feeding vascular branch. This activity required local NO signaling and occurred by means of direct coupling via gap junctions. By contrast, bath application of NO or diabetes, a common microvascular pathology, not only weakened the vascular signaling but also abolished its directionality. We conclude that the exclusivity of neurovascular interactions may thus establish spatial accuracy of blood delivery with the precision of the neuronal receptive field size, and is disrupted early in diabetes.
Old dogs, new trick: classic cancer therapies activate cGAS
Authors: Yum Seoyun , Li Minghao , Chen Zhijian J.
Published: June 2020

The discovery of cancer immune surveillance and immunotherapy has opened up a new era of cancer treatment. Immunotherapies modulate a patient’s immune system to specifically eliminate cancer cells; thus, it is considered a very different approach from classic cancer therapies that usually induce DNA damage to cause cell death in a cell-intrinsic manner. However, recent studies have revealed that classic cancer therapies such as radiotherapy and chemotherapy also elicit antitumor immunity, which plays an essential role in their therapeutic efficacy. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream effector Stimulator of Interferon Genes (STING) have been determined to be critical for this interplay. Here, we review the antitumor roles of the cGAS-STING pathway during tumorigenesis, cancer immune surveillance, and cancer therapies. We also highlight classic cancer therapies that elicit antitumor immune responses through cGAS activation.
A library of ab initio Raman spectra for automated identification of 2D materials
Authors: Taghizadeh Alireza , Leffers Ulrik , Pedersen Thomas G. , Thygesen Kristian S.
Published: June 2020

Raman spectroscopy is frequently used to identify composition, structure and layer thickness of 2D materials. Here, we describe an efficient first-principles workflow for calculating resonant first-order Raman spectra of solids within third-order perturbation theory employing a localized atomic orbital basis set. The method is used to obtain the Raman spectra of 733 different monolayers selected from the Computational 2D Materials Database (C2DB). We benchmark the computational scheme against available experimental data for 15 known monolayers. Furthermore, we propose an automatic procedure for identifying a material based on an input experimental Raman spectrum and apply it to the cases of MoS2 (H-phase) and WTe2 (T$${}^{\prime}$$

′

-phase). The Raman spectra of all materials at different excitation frequencies and polarization configurations are freely available from the C2DB. Our comprehensive and easily accessible library of ab initio Raman spectra should be valuable for both theoreticians and experimentalists in the field of 2D materials.
BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice
Authors: Perkail Stephanie , Andricovich Jaclyn , Kai Yan , Tzatsos Alexandros
Published: June 2020

Chronic pancreatitis represents a risk factor for the development of pancreatic cancer. We find that heterozygous loss of histone H2A lysine 119 deubiquitinase BAP1 (BRCA1 Associated Protein-1) associates with a history of chronic pancreatitis and occurs in 25% of pancreatic ductal adenocarcinomas and 40% of acinar cell carcinomas. Deletion or heterozygous loss of Bap1 in murine pancreata causes genomic instability, tissue damage, and pancreatitis with full penetrance. Concomitant expression of KrasG12D leads to predominantly intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, while pancreatic intraepithelial neoplasias are rarely detected. These lesions progress to metastatic pancreatic cancer with high frequency. Lesions with histological features mimicking Acinar Cell Carcinomas are also observed in some tumors. Heterozygous mice also develop pancreatic cancer suggesting a haploinsufficient tumor suppressor role for BAP1. Mechanistically, BAP1 regulates genomic stability, in a catalytic independent manner, and its loss confers sensitivity to irradiation and platinum-based chemotherapy in pancreatic cancer.
Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
Authors: McNeill Eoin P. , Zeitouni Suzanne , Pan Simin , Haskell Andrew , Cesarek Michael , Tahan Daniel , Clough Bret H. , Krause Ulf , Dobson Lauren K. , Garcia Mayra , Kung Christopher , Zhao Qingguo , Saunders W. Brian , Liu Fei , Kaunas Roland , Gregory Carl A.
Published: June 2020

Approximately 10% of fractures will not heal without intervention. Current treatments can be marginally effective, costly, and some have adverse effects. A safe and manufacturable mimic of anabolic bone is the primary goal of bone engineering, but achieving this is challenging. Mesenchymal stem cells (MSCs), are excellent candidates for engineering bone, but lack reproducibility due to donor source and culture methodology. The need for a bioactive attachment substrate also hinders progress. Herein, we describe a highly osteogenic MSC line generated from induced pluripotent stem cells that generates high yields of an osteogenic cell-matrix (ihOCM) in vitro. In mice, the intrinsic osteogenic activity of ihOCM surpasses bone morphogenic protein 2 (BMP2) driving healing of calvarial defects in 4 weeks by a mechanism mediated in part by collagen VI and XII. We propose that ihOCM may represent an effective replacement for autograft and BMP products used commonly in bone tissue engineering.
Tug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement
Authors: Sakamoto Ryota , Tanabe Masatoshi , Hiraiwa Tetsuya , Suzuki Kazuya , Ishiwata Shin’ichi , Maeda Yusuke T. , Miyazaki Makito
Published: June 2020

Symmetric or asymmetric positioning of intracellular structures including the nucleus and mitotic spindle steers various biological processes such as cell migration, division, and embryogenesis. In typical animal cells, both a sparse actomyosin meshwork in the cytoplasm and a dense actomyosin cortex underneath the cell membrane participate in the intracellular positioning. However, it remains unclear how these coexisting actomyosin structures regulate the positioning symmetry. To reveal the potential mechanism, we construct an in vitro model composed of cytoplasmic extracts and nucleus-like clusters confined in droplets. Here we find that periodic centripetal actomyosin waves contract from the droplet boundary push clusters to the center in large droplets, while network percolation of bulk actomyosin pulls clusters to the edge in small droplets. An active gel model quantitatively reproduces molecular perturbation experiments, which reveals that the tug-of-war between two distinct actomyosin networks with different maturation time-scales determines the positioning symmetry.
Conditional teleportation of quantum-dot spin states
Authors: Qiao Haifeng , Kandel Yadav P. , Manikandan Sreenath K. , Jordan Andrew N. , Fallahi Saeed , Gardner Geoffrey C. , Manfra Michael J. , Nichol John M.
Published: June 2020

Among the different platforms for quantum information processing, individual electron spins in semiconductor quantum dots stand out for their long coherence times and potential for scalable fabrication. The past years have witnessed substantial progress in the capabilities of spin qubits. However, coupling between distant electron spins, which is required for quantum error correction, presents a challenge, and this goal remains the focus of intense research. Quantum teleportation is a canonical method to transmit qubit states, but it has not been implemented in quantum-dot spin qubits. Here, we present evidence for quantum teleportation of electron spin qubits in semiconductor quantum dots. Although we have not performed quantum state tomography to definitively assess the teleportation fidelity, our data are consistent with conditional teleportation of spin eigenstates, entanglement swapping, and gate teleportation. Such evidence for all-matter spin-state teleportation underscores the capabilities of exchange-coupled spin qubits for quantum-information transfer.
Giant spin hydrodynamic generation in laminar flow
Authors: Takahashi R. , Chudo H. , Matsuo M. , Harii K. , Ohnuma Y. , Maekawa S. , Saitoh E.
Published: June 2020

Hydrodynamic motion can generate a flux of electron-spin’s angular momentum via the coupling between fluid rotation and electron spins. Such hydrodynamic generation, called spin hydrodynamic generation (SHDG), has recently attracted attention in a wide range of fields, especially in spintronics. Spintronics deals with spin-mediated interconversion taking place on a micro or nano scale because of the spin-diffusion length scale. To be fully incorporated into the interconversion, SHDG physics should also be established in such a minute scale, where most fluids exhibit a laminar flow. Here, we report electric voltage generation due to the SHDG in a laminar flow of a liquid-metal mercury. The experimental results show a scaling rule unique to the laminar-flow SHDG. Furthermore, its energy conversion efficiency turns out to be about 105 greater than of the turbulent one. Our findings reveal that the laminar-flow SHDG is suitable to downsizing and to extend the coverage of fluid spintronics.
Versatile construction of van der Waals heterostructures using a dual-function polymeric film
Authors: Huang Zhujun , Alharbi Abdullah , Mayer William , Cuniberto Edoardo , Taniguchi Takashi , Watanabe Kenji , Shabani Javad , Shahrjerdi Davood
Published: June 2020

The proliferation of van der Waals (vdW) heterostructures formed by stacking layered materials can accelerate scientific and technological advances. Here, we report a strategy for constructing vdW heterostructures through the interface engineering of the exfoliation substrate using a sub-5 nm polymeric film. Our construction method has two main features that distinguish it from existing techniques. First is the consistency of its exfoliation process in increasing the yield and in producing large (>10,000 μm2) monolayer graphene. Second is the applicability of its layer transfer process to different layered materials without requiring a specialized stamp—a feature useful for generalizing the assembly process. We demonstrate vdW graphene devices with peak carrier mobility of 200,000 and 800,000 cm2 V−1 s−1 at room temperature and 9 K, respectively. The simplicity of our construction method and its versatility to different layered materials may open doors for automating the fabrication process of vdW heterostructures.
Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20
Authors: Wasilko David Jonathan , Johnson Zachary Lee , Ammirati Mark , Che Ye , Griffor Matthew C. , Han Seungil , Wu Huixian
Published: June 2020

Chemokines are important protein-signaling molecules that regulate various immune responses by activating chemokine receptors which belong to the G protein-coupled receptor (GPCR) superfamily. Despite the substantial progression of our structural understanding of GPCR activation by small molecule and peptide agonists, the molecular mechanism of GPCR activation by protein agonists remains unclear. Here, we present a 3.3-Å cryo-electron microscopy structure of the human chemokine receptor CCR6 bound to its endogenous ligand CCL20 and an engineered Go. CCL20 binds in a shallow extracellular pocket, making limited contact with the core 7-transmembrane (TM) bundle. The structure suggests that this mode of binding induces allosterically a rearrangement of a noncanonical toggle switch and the opening of the intracellular crevice for G protein coupling. Our results demonstrate that GPCR activation by a protein agonist does not always require substantial interactions between ligand and the 7TM core region.
Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth
Authors: Howe Erin N. , Burnette Miranda D. , Justice Melanie E. , Schnepp Patricia M. , Hedrick Victoria , Clancy James W. , Guldner Ian H. , Lamere Alicia T. , Li Jun , Aryal Uma K. , D’Souza-Schorey Crislyn , Zartman Jeremiah J. , Zhang Siyuan
Published: June 2020

Breast cancer brain metastases (BCBM) have a 5-20 year latency and account for 30% of mortality; however, mechanisms governing adaptation to the brain microenvironment remain poorly defined. We combine time-course RNA-sequencing of BCBM development with a Drosophila melanogaster genetic screen, and identify Rab11b as a functional mediator of metastatic adaptation. Proteomic analysis reveals that Rab11b controls the cell surface proteome, recycling proteins required for successful interaction with the microenvironment, including integrin β1. Rab11b-mediated control of integrin β1 surface expression allows efficient engagement with the brain ECM, activating mechanotransduction signaling to promote survival. Lipophilic statins prevent membrane association and activity of Rab11b, and we provide proof-of principle that these drugs prevent breast cancer adaptation to the brain microenvironment. Our results identify Rab11b-mediated recycling of integrin β1 as regulating BCBM, and suggest that the recycleome, recycling-based control of the cell surface proteome, is a previously unknown driver of metastatic adaptation and outgrowth.
Efficient wettability-controlled electroreduction of CO2 to CO at Au/C interfaces
Authors: Shi Run , Guo Jiahao , Zhang Xuerui , Waterhouse Geoffrey I. N. , Han Zhaojun , Zhao Yunxuan , Shang Lu , Zhou Chao , Jiang Lei , Zhang Tierui
Published: June 2020

The electrochemical CO2 reduction reaction (CO2RR) represents a very promising future strategy for synthesizing carbon-containing chemicals in a more sustainable way. In spite of great progress in electrocatalyst design over the last decade, the critical role of wettability-controlled interfacial structures for CO2RR remains largely unexplored. Here, we systematically modify the structure of gas-liquid-solid interfaces over a typical Au/C gas diffusion electrode through wettability modification to reveal its contribution to interfacial CO2 transportation and electroreduction. Based on confocal laser scanning microscopy measurements, the Cassie-Wenzel coexistence state is demonstrated to be the ideal three phase structure for continuous CO2 supply from gas phase to Au active sites at high current densities. The pivotal role of interfacial structure for the stabilization of the interfacial CO2 concentration during CO2RR is quantitatively analysed through a newly-developed in-situ fluorescence electrochemical spectroscopic method, pinpointing the necessary CO2 mass transfer conditions for CO2RR operation at high current densities.
Applying lessons from the Ebola vaccine experience for SARS-CoV-2 and other epidemic pathogens
Authors: Wolf Jayanthi , Bruno Samantha , Eichberg Michael , Jannat Risat , Rudo Sharon , VanRheenen Susan , Coller Beth-Ann
Published: June 2020

The world is experiencing an unprecedented global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Development of new vaccines and therapeutics are important to achieve long-term prevention and control of the virus. Experience gained in the development of vaccines for Ebola virus disease provide important lessons in the regulatory, clinical, and manufacturing process that can be applied to SARS-CoV-2 and other epidemic pathogens. This report outlines the main lessons learned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) during development of an Ebola Zaire vaccine (ERVEBO®) and looks ahead to critical lessons beyond vaccine development. It highlights focus areas for public-private partnership and regulatory harmonization that can be directly applied to current vaccine development efforts for SARS-CoV-2, while drawing attention to the need for parallel consideration of issues beyond development that are equally important to achieve global preparedness and response goals.
Influence of sulfate on anion exchange membranes in reverse electrodialysis
Authors: Pintossi Diego , Chen Chieh-Li , Saakes Michel , Nijmeijer Kitty , Borneman Zandrie
Published: June 2020

Reverse electrodialysis (RED) is a technology producing renewable energy from the mixing of river and seawater. In natural salinity gradients, multivalent ions are present, which lead to a reduced RED power output. Transport of multivalent ions against the concentration gradient and their trapping inside the membranes leads to a lower driving force and increased membrane resistance. The present work focuses on the effect of sulfate ions on anion exchange membranes in RED. A monovalent ion selective membrane ability to retain a higher open circuit voltage is offset by the higher resistance in the presence of sulfate, leading to losses in normalized power outputs (−25%) comparable to a standard grade membrane. Longer term experiments revealed that membrane resistance increases over time. This study highlights the need to address uphill transport, resistance increase, and decreased permselectivity of anion exchange membranes in presence of multivalent ions.
Neural and physiological data from participants listening to affective music
Authors: Daly Ian , Nicolaou Nicoletta , Williams Duncan , Hwang Faustina , Kirke Alexis , Miranda Eduardo , Nasuto Slawomir J.
Published: June 2020

Music provides a means of communicating affective meaning. However, the neurological mechanisms by which music induces affect are not fully understood. Our project sought to investigate this through a series of experiments into how humans react to affective musical stimuli and how physiological and neurological signals recorded from those participants change in accordance with self-reported changes in affect. In this paper, the datasets recorded over the course of this project are presented, including details of the musical stimuli, participant reports of their felt changes in affective states as they listened to the music, and concomitant recordings of physiological and neurological activity. We also include non-identifying meta data on our participant populations for purposes of further exploratory analysis. This data provides a large and valuable novel resource for researchers investigating emotion, music, and how they affect our neural and physiological activity.