bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractDespite 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

AbstractSemiconductor 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

AbstractPendrin 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

AbstractMany 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

AbstractSeveral 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

AbstractThe 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

AbstractThe 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

AbstractA 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

AbstractCurrently, 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

AbstractWe 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

AbstractWe 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

AbstractLimb 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

AbstractWe 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

AbstractThe 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.