bluuebunny/crossref_metadata_2025 huggingface dataset:
General Intelligence and the Dark Triad
Authors: Michels Moritz
Published: July 2021

Abstract. The dark triad of personality (D3) – consisting of psychopathy, Machiavellianism, and narcissism – is a set of socially aversive personality traits. All three traits encompass disagreeable behavior and a particular disregard for the well-being of others, but also a tendency to strategic and deceptive manipulation of social environments in order to attain one′s goals. To exercise these complex manipulations effectively it seems beneficial to have high cognitive abilities. Therefore, a meta-analysis was conducted to examine possible relationships between intelligence and the dark triad. A total of 143 studies were identified to estimate the strength of relationships between the D3 and general, verbal, and nonverbal intelligence. The results indicate that none of the constructs of the dark triad are meaningfully related to intelligence. However, there was a small negative correlation between intelligence and Factor 2 psychopathy. The substantial heterogeneity regarding the observed effect sizes could not be explained with meta-regression for the most part. There was no evidence for a publication bias. In total, the results challenge the notion that the dark triad is an adaptive set of personality traits that enables individuals to effectively manipulate their social surroundings.
Periodic Variations in Solar Wind and Responses of the Magnetosphere and Thermosphere in March 2017
Authors: Zhang Yongliang , Paxton Larry , Wang Wenbin , Huang Chaosong
Published: July 2021

TIMED/GUVI observed thermospheric column ∑O/N2 depletion in both hemispheres between March 1 and 21, 2017 which was caused by large periodic variations in interplanetary magnetic field (IMF) and a high solar wind speed, likely in a solar wind. The dominant periods seen in the solar wind and magnetosphere coupling function (CF) were around 1.9, 3.0, 4.7, 7.6, 14.0 and 22.0 h on March 1 and 2. The major AE variations were around 3.0, 4.7, 7.6, 10.7, 14.0 and 22.0 h. Auroral hemispheric power (HP) also showed periodic variations similar to that of AE, except for the absence of the 3.0 h variation due to a low sampling rate in HP data. SymH data didn't show the periodic variations seen in AE but a weak 12‐h periodic variation which was seen in the solar wind dynamic pressure. A weak AE and HP variation at 10.7‐h period was not observed in CF or any individual solar wind parameters or IMF components. These results suggest that (a) the oscillating IMF pumped energy and mass periodically into the magnetosphere and the polar ionosphere, creating a long lasting (20‐days) storm and O/N2 depletion, (b) the high latitude AE and HP responded to the solar wind and IMF variations directly, (c) SymH did not show any direct periodic responses, likely due to the fact that the ring current response resulted from the cumulative effect of solar wind and IMF drivers, (d) the 10.7‐h variations in AE and HP were likely due to magnetospheric internal processes.
Free Infragravity Waves in the North Sea
Authors: Rijnsdorp Dirk P. , Reniers Ad J. H. M. , Zijlema Marcel
Published: July 2021

Infragravity waves are low‐frequency surface waves that can impact a variety of nearshore and oceanic processes. Recent measurements in the North Sea showed that significant bursts of infragravity energy occurred during storm events. Using a spectral wave model, we show that a substantial part of this energy was radiated from distant shorelines where it was generated by the incident sea‐swell waves. These radiated infragravity waves can cross the North Sea basin and reach distant shorelines. The origin of the infragravity wave energy varied between the different storms, and particularly depends on where largest sea‐swell waves made landfall. Along the coastlines of the North Sea, shoreward directed infragravity waves that originate from a remote source were non‐negligible during storm events. This suggests that radiated infragravity waves can potentially contribute to coastal dynamics and hazards away from their region of generation.
GEM Workshop on Intercalibrating Cusp Signatures
Authors: Anonymous
Published: July 2021

On October 9, 1990, a lively group of more than 60 scientists from around the world gathered at Northeastern University's Henderson House in Weston, Mass., to spend 4 days in concentrated efforts to unravel the complexities of cusp/cleft theory and observations.

Plans for the National Science Foundation‐sponsored workshop were formulated at the previous GEM workshop convened by Ted Rosenberg at the University of Maryland in October 1989, where participants agreed that the first task of the first GEM campaign—attacking problems of the magnetopause, boundary layers, and their signatures in the ionosphere—should be the identification of cusp signatures in ground‐based and airborne data by intercalibrating with spacecraft data on direct overflights.
The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis
Authors: Tran Tiffany M. , Philipp Julia , Bassi Jaspal Singh , Nibber Neha , Draper Jolene M. , Lin Tasha L. , Palanichamy Jayanth Kumar , Jaiswal Amit Kumar , Silva Oscar , Paing May , King Jennifer , Katzman Sol , Sanford Jeremy R. , Rao Dinesh S.
Published: July 2021

Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.
Uncovering recent progress in nanostructured light-emitters for information and communication technologies
Authors: Grillot Frédéric , Duan Jianan , Dong Bozhang , Huang Heming
Published: July 2021

Semiconductor nanostructures with low dimensionality like quantum dots and quantum dashes are one of the best attractive and heuristic solutions for achieving high performance photonic devices. When one or more spatial dimensions of the nanocrystal approach the de Broglie wavelength, nanoscale size effects create a spatial quantization of carriers leading to a complete discretization of energy levels along with additional quantum phenomena like entangled-photon generation or squeezed states of light among others. This article reviews our recent findings and prospects on nanostructure based light emitters where active region is made with quantum-dot and quantum-dash nanostructures. Many applications ranging from silicon-based integrated technologies to quantum information systems rely on the utilization of such laser sources. Here, we link the material and fundamental properties with the device physics. For this purpose, spectral linewidth, polarization anisotropy, optical nonlinearities as well as microwave, dynamic and nonlinear properties are closely examined. The paper focuses on photonic devices grown on native substrates (InP and GaAs) as well as those heterogeneously and epitaxially grown on silicon substrate. This research pipelines the most exciting recent innovation developed around light emitters using nanostructures as gain media and highlights the importance of nanotechnologies on industry and society especially for shaping the future information and communication society.
Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism
Authors: Ochiai-Homma Fumika , Kuribayashi-Okuma Emiko , Tsurutani Yuya , Ishizawa Kenichi , Fujii Wataru , Odajima Kohei , Kawagoe Mika , Tomomitsu Yoshihiro , Murakawa Masataka , Asakawa Shinichiro , Hirohama Daigoro , Nagura Michito , Arai Shigeyuki , Yamazaki Osamu , Tamura Yoshifuru , Fujigaki Yoshihide , Nishikawa Tetsuo , Shibata Shigeru
Published: July 2021

Pendrin is a Cl−/HCO3− exchanger selectively present in the intercalated cells of the kidney. Although experimental studies have demonstrated that pendrin regulates blood pressure downstream of the renin-angiotensin-aldosterone system, its role in human hypertension remains unclear. Here, we analyzed the quantitative changes in pendrin in urinary extracellular vesicles (uEVs) isolated from a total of 30 patients with primary aldosteronism (PA) and from a rat model of aldosterone excess. Western blot analysis revealed that pendrin is present in dimeric and monomeric forms in uEVs in humans and rats. In a rodent model that received continuous infusion of aldosterone with or without concomitant administration of the selective mineralocorticoid receptor (MR) antagonist esaxerenone, pendrin levels in uEVs, as well as those of epithelial Na+ channel (ENaC) and Na-Cl-cotransporter (NCC), were highly correlated with renal abundance. In patients with PA, pendrin levels in uEVs were reduced by 49% from baseline by adrenalectomy or pharmacological MR blockade. Correlation analysis revealed that the magnitude of pendrin reduction after treatment significantly correlated with the baseline aldosterone-renin ratio (ARR). Finally, a cross-sectional analysis of patients with PA confirmed a significant correlation between the ARR and pendrin levels in uEVs. These data are consistent with experimental studies showing the role of pendrin in aldosterone excess and suggest that pendrin abundance is attenuated by therapeutic interventions in human PA. Our study also indicates that pendrin analysis in uEVs, along with other proteins, can be useful to understand the pathophysiology of hypertensive disorders.
The mortality cost of carbon
Authors: Bressler R. Daniel
Published: July 2021

Many studies project that climate change can cause a significant number of excess deaths. Yet, in integrated assessment models (IAMs) that determine the social cost of carbon (SCC) and prescribe optimal climate policy, human mortality impacts are limited and not updated to the latest scientific understanding. This study extends the DICE-2016 IAM to explicitly include temperature-related mortality impacts by estimating a climate-mortality damage function. We introduce a metric, the mortality cost of carbon (MCC), that estimates the number of deaths caused by the emissions of one additional metric ton of CO2. In the baseline emissions scenario, the 2020 MCC is 2.26 × 10‒4[low to high estimate −1.71× 10‒4to 6.78 × 10‒4] excess deaths per metric ton of 2020 emissions. This implies that adding 4,434 metric tons of carbon dioxide in 2020—equivalent to the lifetime emissions of 3.5 average Americans—causes one excess death globally in expectation between 2020-2100. Incorporating mortality costs increases the 2020 SCC from $37 to $258 [−$69 to $545] per metric ton in the baseline emissions scenario. Optimal climate policy changes from gradual emissions reductions starting in 2050 to full decarbonization by 2050 when mortality is considered.
Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers
Authors: Jeewandara Chandima , Kamaladasa Achala , Pushpakumara Pradeep Darshana , Jayathilaka Deshni , Aberathna Inoka Sepali , Danasekara Danasekara Rallage Saubhagya Rasika , Guruge Dinuka , Ranasinghe Thushali , Dayarathna Shashika , Pathmanathan Thilagaraj , Somathilake Gayasha , Deshan Madhusanka Panambara Arachchige , Ramu Shyrar Tanussiya , Pramanayagam Jayadas Tibutius Thanesh , Kuruppu Heshan , Wijesinghe Ayesha , Thashmi Nimasha Herath Mudiyanselage , Milroy Dushantha , Nandasena Achini Anuja , Nilanka Sanjeewani Poththawela Kankanam Gamage , Wijayamuni Ruwan , Samaraweera Sudath , Schimanski Lisa , Tan T. K. , Dong Tao , Ogg Graham S. , Townsend Alain , Malavige Gathsaurie Neelika
Published: July 2021

Several COVID-19 vaccines have received emergency approval. Here we assess the immunogenicity of a single dose of the AZD1222 vaccine, at one month, in a cohort of health care workers (HCWs) (629 naïve and 26 previously infected). 93.4% of naïve HCWs seroconverted, irrespective of age and gender. Haemagglutination test for antibodies to the receptor binding domain (RBD), surrogate neutralization assay (sVNT) and ex vivo IFNγ ELISpot assays were carried out in a sub-cohort. ACE2 blocking antibodies (measured by sVNT) were detected in 67/69 (97.1%) of naïve HCWs. Antibody levels to the RBD of the wild-type virus were higher than to RBD of B.1.1.7, and titres to B.1.351 were very low. Ex vivo T cell responses were observed in 30.8% to 61.7% in naïve HCWs. Previously infected HCWs, developed significantly higher (p < 0.0001) ACE2 blocking antibodies and antibodies to the RBD for the variants B.1.1.7 and B.1.351. This study shows high seroconversion after one vaccine dose, but also suggests that one vaccine dose may be insufficient to protect against emerging variants.
Simultaneous construction of axial and planar chirality by gold/TY-Phos-catalyzed asymmetric hydroarylation
Authors: Zhang Pei-Chao , Li Yin-Lin , He Jiafeng , Wu Hai-Hong , Li Zhiming , Zhang Junliang
Published: July 2021

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. Herein a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocenes derivatives is developed, which enable the simultaneous construction of axial and planar chirality. The here identified TY-Phos derived gold complex is responsible for the high yield, good diastereoselectivity (>20:1 dr), high enantioselectivities (up to 99% ee) and mild conditions. The catalyst system also shows potential application in the synthesis of chiral biaryl compounds. The cause of high enantioselectivity of this hydroarylation is investigated with density functional theory caculation.
Inhibitory gating of coincidence-dependent sensory binding in secondary auditory cortex
Authors: Kline Amber M. , Aponte Destinee A. , Tsukano Hiroaki , Giovannucci Andrea , Kato Hiroyuki K.
Published: July 2021

Abstract

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech. This “feature binding” relies on the precise synchrony of each component’s onset timing, but little is known regarding its neural correlates. We find that multi-frequency sounds prevalent in vocalizations, specifically harmonics, preferentially activate the mouse secondary auditory cortex (A2), whose response deteriorates with shifts in component onset timings. The temporal window for harmonics integration in A2 was broadened by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Importantly, A2 has functionally connected subnetworks of neurons preferentially encoding harmonic over inharmonic sounds. These subnetworks are stable across days and exist prior to experimental harmonics exposure, suggesting their formation during development. Furthermore, A2 inactivation impairs performance in a discrimination task for coincident harmonics. Together, we propose A2 as a locus for multi-frequency integration, which may form the circuit basis for vocal processing.
Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity
Authors: Zhang Yi , Brown Kyle , Yu Yucong , Ibrahim Ziad , Zandian Mohamad , Xuan Hongwen , Ingersoll Steven , Lee Thomas , Ebmeier Christopher C. , Liu Jiuyang , Panne Daniel , Shi Xiaobing , Ren Xiaojun , Kutateladze Tatiana G.
Published: July 2021

The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.
A therapeutic vascular conduit to support in vivo cell-secreted therapy
Authors: Han Edward X. , Qian Hong , Jiang Bo , Figetakis Maria , Kosyakova Natalia , Tellides George , Niklason Laura E. , Chang William G.
Published: July 2021

A significant barrier to implementation of cell-based therapies is providing adequate vascularization to provide oxygen and nutrients. Here we describe an approach for cell transplantation termed the Therapeutic Vascular Conduit (TVC), which uses an acellular vessel as a scaffold for a hydrogel sheath containing cells designed to secrete a therapeutic protein. The TVC can be directly anastomosed as a vascular graft. Modeling supports the concept that the TVC allows oxygenated blood to flow in close proximity to the transplanted cells to prevent hypoxia. As a proof-of-principle study, we used erythropoietin (EPO) as a model therapeutic protein. If implanted as an arteriovenous vascular graft, such a construct could serve a dual role as an EPO delivery platform and hemodialysis access for patients with end-stage renal disease. When implanted into nude rats, TVCs containing EPO-secreting fibroblasts were able to increase serum EPO and hemoglobin levels for up to 4 weeks. However, constitutive EPO expression resulted in macrophage infiltration and luminal obstruction of the TVC, thus limiting longer-term efficacy. Follow-up in vitro studies support the hypothesis that EPO also functions to recruit macrophages. The TVC is a promising approach to cell-based therapeutic delivery that has the potential to overcome the oxygenation barrier to large-scale cellular implantation and could thus be used for a myriad of clinical disorders. However, a complete understanding of the biological effects of the selected therapeutic is absolutely essential.
Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach
Authors: Mahmud Shafi , Rafi Md. Oliullah , Paul Gobindo Kumar , Promi Maria Meha , Shimu Mst. Sharmin Sultana , Biswas Suvro , Emran Talha Bin , Dhama Kuldeep , Alyami Salem A. , Moni Mohammad Ali , Saleh Md. Abu
Published: July 2021

Currently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.
Mineralogical and chemical properties inversed from 21-lunar-day VNIS observations taken during the Chang’E-4 mission
Authors: Zeng Qinghong , Chen Shengbo , Zhang Yuanzhi , Mu Yongling , Dai Rui , Yang Congyu , Li Anzhen , Lu Peng
Published: July 2021

We report on the mineralogical and chemical properties of materials investigated by the lunar rover Yutu-2, which landed on the Von Kármán crater in the pre-Nectarian South Pole–Aitken (SPA) basin. Yutu-2 carried several scientific payloads, including the Visible and Near-infrared Imaging Spectrometer (VNIS), which is used for mineral identification, offering insights into lunar evolution. We used 86 valid VNIS data for 21 lunar days, with mineral abundance obtained using the Hapke radiative transfer model and sparse unmixing algorithm and chemical compositions empirically estimated. The mineralogical properties of the materials at the Chang’E-4 (CE-4) site referred to as norite/gabbro, based on findings of mineral abundance, indicate that they may be SPA impact melt components excavated by a surrounding impact crater. We find that CE-4 materials are dominated by plagioclase and pyroxene and feature little olivine, with 50 of 86 observations showing higher LCP than HCP in pyroxene. In view of the effects of space weathering, olivine content may be underestimated, with FeO and TiO2 content estimated using the maturity-corrected method. Estimates of chemical content are 7.42–18.82 wt% FeO and 1.48–2.1 wt% TiO2, with a low-medium Mg number (Mg # ~ 55). Olivine-rich materials are not present at the CE-4 landing site, based on the low-medium Mg #. Multi-origin materials at the CE-4 landing site were analyzed with regard to concentrations of FeO and TiO2 content, supporting our conclusion that the materials at CE-4 do not have a single source but rather are likely a mixture of SPA impact melt components excavated by surrounding impact crater and volcanic product ejecta.
Towards practical applications of quantum emitters in boron nitride
Authors: Koperski M. , Pakuła K. , Nogajewski K. , Dąbrowska A. K. , Tokarczyk M. , Pelini T. , Binder J. , Fąs T. , Suffczyński J. , Stępniewski R. , Wysmołek A. , Potemski M.
Published: July 2021

We demonstrate quantum emission capabilities from boron nitride structures which are relevant for practical applications and can be seamlessly integrated into a variety of heterostructures and devices. First, the optical properties of polycrystalline BN films grown by metalorganic vapour-phase epitaxy are inspected. We observe that these specimens display an antibunching in the second-order correlation functions, if the broadband background luminescence is properly controlled. Furthermore, the feasibility to use flexible and transparent substrates to support hBN crystals that host quantum emitters is explored. We characterise hBN powders deposited onto polydimethylsiloxane films, which display quantum emission characteristics in ambient environmental conditions.
Feasibility of generating 90 Hz vibrations in remote implanted magnets
Authors: Montero Jordan , Clemente Francesco , Cipriani Christian
Published: July 2021

Limb amputation not only reduces the motor abilities of an individual, but also destroys afferent channels that convey essential sensory information to the brain. Significant efforts have been made in the area of upper limb prosthetics to restore sensory feedback, through the stimulation of residual sensory elements. Most of the past research focused on the replacement of tactile functions. On the other hand, the difficulties in eliciting proprioceptive sensations using either haptic or (neural) electrical stimulation, has limited researchers to rely on sensory substitution. Here we propose the myokinetic stimulation interface, that aims at restoring natural proprioceptive sensations by exploiting the so-called tendon illusion, elicited through the vibration of magnets implanted inside residual muscles. We present a prototype which exploits 12 electromagnetic coils to vibrate up to four magnets implanted in a forearm mockup. The results demonstrated that it is possible to generate highly directional and frequency-selective vibrations. The system proved capable of activating a single magnet, out of many. Hence, this interface constitutes a promising approach to restore naturally perceived proprioception after an amputation. Indeed, by implanting several magnets in independent muscles, it would be possible to restore proprioceptive sensations perceived as coming from single digits.
Higher-order temporal network effects through triplet evolution
Authors: Yao Qing , Chen Bingsheng , Evans Tim S. , Christensen Kim
Published: July 2021

We study the evolution of networks through ‘triplets’—three-node graphlets. We develop a method to compute a transition matrix to describe the evolution of triplets in temporal networks. To identify the importance of higher-order interactions in the evolution of networks, we compare both artificial and real-world data to a model based on pairwise interactions only. The significant differences between the computed matrix and the calculated matrix from the fitted parameters demonstrate that non-pairwise interactions exist for various real-world systems in space and time, such as our data sets. Furthermore, this also reveals that different patterns of higher-order interaction are involved in different real-world situations. To test our approach, we then use these transition matrices as the basis of a link prediction algorithm. We investigate our algorithm’s performance on four temporal networks, comparing our approach against ten other link prediction methods. Our results show that higher-order interactions in both space and time play a crucial role in the evolution of networks as we find our method, along with two other methods based on non-local interactions, give the best overall performance. The results also confirm the concept that the higher-order interaction patterns, i.e., triplet dynamics, can help us understand and predict the evolution of different real-world systems.
Association between central non-dipping pattern and platelet morphology in adults with type 1 diabetes without cardiovascular disease: a cross-sectional study
Authors: Kulecki Michal , Naskret Dariusz , Kaminski Mikolaj , Kasprzak Dominika , Lachowski Pawel , Klause Daria , Kozlowska Maria , Flotynska Justyna , Uruska Aleksandra , Zozulinska-Ziolkiewicz Dorota
Published: July 2021

The non-dipping pattern is nighttime systolic blood pressure (SBP) fall of less than 10%. Several studies showed that the non-dipping pattern, increased mean platelet volume (MPV), and platelet distribution width (PDW) are associated with elevated cardiovascular risk. Hypertensives with the non-dipping pattern have higher MPV than the dippers but this relationship was never investigated among people with type 1 diabetes mellitus (T1DM). This study aimed to investigate the association between the central dipping pattern and platelet morphology in T1DM subjects. We measured the central and brachial blood pressure with a validated non-invasive brachial oscillometric device—Arteriograph 24—during twenty-four-hour analysis in T1DM subjects without diagnosed hypertension. The group was divided based on the central dipping pattern for the dippers and the non-dippers. From a total of 62 subjects (32 males) aged 30.1 (25.7–37) years with T1DM duration 15.0 (9.0–20) years, 36 were non-dippers. The non-dipper group had significantly higher MPV (MPV (10.8 [10.3–11.5] vs 10.4 [10.0–10.7] fl; p = 0.041) and PDW (13.2 [11.7–14.9] vs 12.3 [11.7–12.8] fl; p = 0.029) than dipper group. Multivariable logistic regression revealed that MPV (OR 3.74; 95% CI 1.48–9.45; p = 0.005) and PDW (OR 1.91; 95% CI 1.22–3.00; p = 0.005) were positively associated with central non-dipping pattern adjusting for age, sex, smoking status, daily insulin intake, and height. MPV and PDW are positively associated with the central non-dipping pattern among people with T1DM.
A piggyBac-based platform for genome editing and clonal rhesus macaque iPSC line derivation
Authors: Rodriguez-Polo Ignacio , Mißbach Sophie , Petkov Stoyan , Mattern Felix , Maierhofer Anna , Grządzielewska Iga , Tereshchenko Yuliia , Urrutia-Cabrera Daniel , Haaf Thomas , Dressel Ralf , Bartels Iris , Behr Rüdiger
Published: July 2021

Non-human primates (NHPs) are, due to their close phylogenetic relationship to humans, excellent animal models to study clinically relevant mutations. However, the toolbox for the genetic modification of NHPs is less developed than those for other species like mice. Therefore, it is necessary to further develop and refine genome editing approaches in NHPs. NHP pluripotent stem cells (PSCs) share key molecular signatures with the early embryo, which is an important target for genomic modification. Therefore, PSCs are a valuable test system for the validation of embryonic genome editing approaches. In the present study, we made use of the versatility of thepiggyBactransposon system for different purposes in the context of NHP stem cell technology and genome editing. These include (1) Robust reprogramming of rhesus macaque fibroblasts to induced pluripotent stem cells (iPSCs); (2) Culture of the iPSCs under feeder-free conditions even after removal of the transgene resulting in transgene-free iPSCs; (3) Development of a CRISPR/Cas-based work-flow to edit the genome of rhesus macaque PSCs with high efficiency; (4) Establishment of a novel protocol for the derivation of gene-edited monoclonal NHP-iPSC lines. These findings facilitate efficient testing of genome editing approaches in NHP-PSC before their in vivo application.
Equatorial pliosaurid from Venezuela marks the youngest South American occurrence of the clade
Authors: Bastiaans Dylan , Madzia Daniel , Carrillo-Briceño Jorge D. , Sachs Sven
Published: July 2021

Pliosaurids were the dominant macropredators in aquatic environments at least since the Middle Jurassic until their extinction in the early Late Cretaceous. Until very recently, the Cretaceous record of Pliosauridae has been poor and difficult to interpret from the taxonomic and phylogenetic perspective. Despite that the knowledge of Cretaceous pliosaurids improved in recent years, numerous aspects of their evolutionary history still remain only poorly known. Here, we report the first pliosaurid material from Venezuela. The taxon is most likely earliest Cenomanian in age, thus representing the youngest occurrence of Pliosauridae from South America. The Venezuelan taxon is based on a well-preserved tooth crown whose morphology and outer enamel structural elements appear to resemble especially those observable in the giant pliosaurid Sachicasaurus vitae from the Lower Cretaceous of Colombia. The new discovery extends the pliosaurid record on the continent by more than 10 million years and likely marks the southernmost Upper Cretaceous occurrence of Pliosauridae, worldwide. We also briefly discuss the affinities of the enigmatic Venezuelan elasmosaurid Alzadasaurus tropicus and highlight similarities to elasmosaurids from the Western Interior Seaway.
Morpho‐metabotyping the oxidative stress response
Authors: Rusz Mate , Del Favero Giorgia , El Abiead Yasin , Gerner Christopher , Keppler Bernhard K. , Jakupec Michael A. , Koellensperger Gunda
Published: July 2021

Oxidative stress and reactive oxygen species (ROS) are central to many physiological and pathophysiological processes. However, due to multiple technical challenges, it is hard to capture a comprehensive readout of the cell, involving both biochemical and functional status. We addressed this problem by developing a fully parallelized workflow for metabolomics (providing absolute quantities for > 100 metabolites including TCA cycle, pentose phosphate pathway, purine metabolism, glutathione metabolism, cysteine and methionine metabolism, glycolysis and gluconeogenesis) and live cell imaging microscopy. The correlative imaging strategy was applied to study morphological and metabolic adaptation of cancer cells upon short-term hydrogen peroxide (H2O2) exposure in vitro. The combination provided rich metabolic information at the endpoint of exposure together with imaging of mitochondrial effects. As a response, superoxide concentrations were elevated with a strong mitochondrial localization, and multi-parametric image analysis revealed a shift towards fragmentation. In line with this, metabolism reflected both the impaired mitochondrial function and shifts to support the first-line cellular defense and compensate for energy loss. The presented workflow combining high-end technologies demonstrates the applicability for the study of short-term oxidative stress, but it can be suitable for the in-depth study of various short-term oxidative and other cellular stress-related phenomena.
Predictors of chronic opioid therapy in Medicaid beneficiaries with HIV who initiated antiretroviral therapy
Authors: Oh GYeon , Brouwer Emily S. , Abner Erin L. , Fardo David W. , Freeman Patricia R. , Delcher Chris , Moga Daniela C.
Published: July 2021

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002–2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with COT. In sex-stratified analyses, multiple predictors were shared between male and female beneficiaries; however, chronic obstructive pulmonary disease, liver disease, any malignancy, and antipsychotic therapy were unique to female beneficiaries. Comorbidities and polypharmacy were important predictors of COT in Medicaid beneficiaries with HIV who initiated cART.
Association of incremental pulse wave velocity with cardiometabolic risk factors
Authors: Nabeel P. M. , Chandran Dinu S. , Kaur Prabhdeep , Thanikachalam Sadagopan , Sivaprakasam Mohanasankar , Joseph Jayaraj
Published: July 2021

We investigate the association of incremental pulse wave velocity (ΔC; the change in pulse wave velocity over a cardiac cycle) with cardiometabolic risk factors and report the first and (currently) the largest population-level data. In a cross-sectional study performed in a cohort of 1373 general population participants, ΔC was measured using clinically validated ARTSENS devices. There were 455 participants in the metabolic syndrome (MetS) group whose average ΔC was ~ 28.4% higher than that of the non-metabolic syndrome (Non-MetS) group. Females with MetS showed ~ 10.9% elevated average ΔC compared to males of the Non-MetS group. As the number of risk factors increased from 0 to 5, the average ΔC escalated by ~ 55% (1.50 ± 0.52 m/s to 2.33 ± 0.91 m/s). A gradual increase in average ΔC was observed across each decade from the younger (ΔC = 1.53 ± 0.54 m/s) to geriatric (ΔC = 2.34 ± 0.59 m/s) populations. There was also a significant difference in ΔC among the blood pressure categories. Most importantly, ΔC ≥ 1.81 m/s predicted a constellation of ≥ 3 risks with AUC = 0.615, OR = 2.309, and RR = 1.703. All statistical trends remained significant, even after adjusting for covariates. The study provides initial evidence for the potential use of ΔC as a tool for the early detection and screening of vascular dysfunction, which opens up avenues for active clinical and epidemiological studies. Further investigations are encouraged to confirm and establish the causative mechanism for the reported associations.
Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
Authors: Marozkina Nadzeya , Smith Laura , Zhao Yi , Zein Joe , Chmiel James F. , Kim Jeeho , Kiselar Janna , Davis Michael D. , Cunningham Rebekah S. , Randell Scott H. , Gaston Benjamin
Published: July 2021

Endothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.
AnnoMiner is a new web-tool to integrate epigenetics, transcription factor occupancy and transcriptomics data to predict transcriptional regulators
Authors: Meiler Arno , Marchiano Fabio , Haering Margaux , Weitkunat Manuela , Schnorrer Frank , Habermann Bianca H.
Published: July 2021

Gene expression regulation requires precise transcriptional programs, led by transcription factors in combination with epigenetic events. Recent advances in epigenomic and transcriptomic techniques provided insight into different gene regulation mechanisms. However, to date it remains challenging to understand how combinations of transcription factors together with epigenetic events control cell-type specific gene expression. We have developed the AnnoMiner web-server, an innovative and flexible tool to annotate and integrate epigenetic, and transcription factor occupancy data. First, AnnoMiner annotates user-provided peaks with gene features. Second, AnnoMiner can integrate genome binding data from two different transcriptional regulators together with gene features. Third, AnnoMiner offers to explore the transcriptional deregulation of genes nearby, or within a specified genomic region surrounding a user-provided peak. AnnoMiner’s fourth function performs transcription factor or histone modification enrichment analysis for user-provided gene lists by utilizing hundreds of public, high-quality datasets from ENCODE for the model organisms human, mouse,DrosophilaandC. elegans. Thus, AnnoMiner can predict transcriptional regulators for a studied process without the strict need for chromatin data from the same process. We compared AnnoMiner to existing tools and experimentally validated several transcriptional regulators predicted by AnnoMiner to indeed contribute to muscle morphogenesis inDrosophila. AnnoMiner is freely available athttp://chimborazo.ibdm.univ-mrs.fr/AnnoMiner/.
Molecular dynamics study on structural and atomic evolution between Au and Ni nanoparticles through coalescence
Authors: Li Bangquan , Li Jing , Su Xiaoqiang , Cui Yimin
Published: July 2021

Motivated by the structure evolution experiments of Janus NiAu nanoparticles (NPs), we present a detailed study on the thermodynamic evolution of Ni and Au NPs with different ratios of Au and Ni through the molecular dynamics (MD) simulations. It is found that, for fixed Ni particle size (5.8 nm in diameter), the energy variation with the increasing temperature is related to the Au sizes (1.5–9.6 nm in diameter), due to the diverse atomic segregation modes. For a small Au particle, due to lattice induction, the structure will change from order to disorder and then to order. The interface defects of the merging NPs could be automatically eliminated by coalescence processes. The change in energy as the temperature increases is similar to that of monometallic NPs. For larger Au particles, the irregular variation of energy occurs and the atomic energy experience one or two reductions at least with the increase of the temperature. The segregation of Au atoms to the surface of Ni particle is dominant during the continuous heating process. The coalescence processes of Au atoms strongly determine the final morphology of the particles. Dumbbell-like, Janus and eccentric core–shell spherical structures could be obtained during the heating process. Our results will provide an effective approach to the design of novel materials with specific properties through thermal control.
Honing in on bioluminescent milky seas from space
Authors: Miller Steven D. , Haddock Steven H. D. , Straka William C. , Seaman Curtis J. , Combs Cynthia L. , Wang Menghua , Shi Wei , Nam SungHyun
Published: July 2021

Milky seas are a rare form of marine bioluminescence where the nocturnal ocean surface produces a widespread, uniform and steady whitish glow. Mariners have compared their appearance to a daylit snowfield that extends to all horizons. Encountered most often in remote waters of the northwest Indian Ocean and the Maritime Continent, milky seas have eluded rigorous scientific inquiry, and thus little is known about their composition, formation mechanism, and role within the marine ecosystem. The Day/Night Band (DNB), a new-generation spaceborne low-light imager, holds potential to detect milky seas, but the capability has yet to be demonstrated. Here, we show initial examples of DNB-detected milky seas based on a multi-year (2012–2021) search. The massive bodies of glowing ocean, sometimes exceeding 100,000 km2 in size, persist for days to weeks, drift within doldrums amidst the prevailing sea surface currents, and align with narrow ranges of sea surface temperature and biomass in a way that suggests water mass isolation. These findings show how spaceborne assets can now help guide research vessels toward active milky seas to learn more about them.
Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas
Authors: Sugiura Yoshiya , Machinami Rikuo , Matsumoto Seiichi , Kanda Hiroaki , Ae Keisuke , Takazawa Yutaka , Takeuchi Kengo
Published: July 2021

It is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.
KBoost: a new method to infer gene regulatory networks from gene expression data
Authors: Iglesias-Martinez Luis F. , De Kegel Barbara , Kolch Walter
Published: July 2021

Reconstructing gene regulatory networks is crucial to understand biological processes and holds potential for developing personalized treatment. Yet, it is still an open problem as state-of-the-art algorithms are often not able to process large amounts of data within reasonable time. Furthermore, many of the existing methods predict numerous false positives and have limited capabilities to integrate other sources of information, such as previously known interactions. Here we introduce KBoost, an algorithm that uses kernel PCA regression, boosting and Bayesian model averaging for fast and accurate reconstruction of gene regulatory networks. We have benchmarked KBoost against other high performing algorithms using three different datasets. The results show that our method compares favorably to other methods across datasets. We have also applied KBoost to a large cohort of close to 2000 breast cancer patients and 24,000 genes in less than 2 h on standard hardware. Our results show that molecularly defined breast cancer subtypes also feature differences in their GRNs. An implementation of KBoost in the form of an R package is available at: https://github.com/Luisiglm/KBoost and as a Bioconductor software package.
Association between short-term heart rate variability and blood coagulation in patients with breast cancer
Authors: Wang Lingling , Wang Jingfeng , Li Peng , Wang Xiangzhi , Wu Shuang , Shi Bo
Published: July 2021

The purpose of this study was to investigate the relationship between heart rate variability (HRV), a non-invasive tool for evaluating autonomic function, and routine coagulation indices (RCIs) in patients with breast cancer (BC). Forty-six BC patients were enrolled in this study. Blood biochemistry tests were performed to extract RCIs, including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Five-minute electrocardiograms were collected for analysis of HRV parameters (SDNN, RMSSD, LF, HF, LF n.u., HF n.u., LF/HF). Multiple linear regression models examined the relationship of HRV parameters with RCIs. RMSSD, LF n.u., HF n.u., LF/HF were significantly associated with PT. Specifically, the value of PT increased by 0.192 ± 0.091 or 0.231 ± 0.088 s, respectively for each 1 standard deviation (SD) increase in RMSSD or HF n.u.; it increased by 0.230 ± 0.088 or 0.215 ± 0.088 s, respectively for each 1 − SD decrease in LF n.u. or ln (LF/HF) (all P < 0.05). RMSSD was significantly associated with APTT, i.e., the value of APTT increased by 1.032 ± 0.470 s for each 1 − SD increase in RMSSD (P < 0.05). HRV parameters were associated with RCIs in patients with BC. These observations suggest that the autonomic nervous system and coagulation indices in BC patients are linked, potentially explaining the reason that they are both associated with the prognosis.