bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demonstration of universal control between non-interacting qubits using the Quantum Zeno effect
Authors: Blumenthal E. , Mor C. , Diringer A. A. , Martin L. S. , Lewalle P. , Burgarth D. , Whaley K. B. , Hacohen-Gourgy S. 
Published: July 2022

AbstractThe Zeno effect occurs in quantum systems when a very strong measurement is applied, which can alter the dynamics in non-trivial ways. Despite being dissipative, the dynamics stay coherent within any degenerate subspaces of the measurement. Here we show that such a measurement can turn a single-qubit operation into a two- or multi-qubit entangling gate, even in a non-interacting system. We demonstrate this gate between two effectively non-interacting transmon qubits. Our Zeno gate works by imparting a geometric phase on the system, conditioned on it lying within a particular non-local subspace. These results show how universality can be generated not only by coherent interactions as is typically employed in quantum information platforms, but also by Zeno measurements.
BMP3 inhibits TGFβ2-mediated myofibroblast differentiation during wound healing of the embryonic cornea
Authors: Spurlin James W. , Garis Matthew R. , Lwigale Peter Y. 
Published: July 2022

AbstractOften acute damage to the cornea initiates drastic tissue remodeling, resulting in fibrotic scarring that disrupts light transmission and precedes vision impairment. Very little is known about the factors that can mitigate fibrosis and promote scar-free cornea wound healing. We previously described transient myofibroblast differentiation during non-fibrotic repair in an embryonic cornea injury model. Here, we sought to elucidate the mechanistic regulation of myofibroblast differentiation during embryonic cornea wound healing. We found that alpha-smooth muscle actin (αSMA)-positive myofibroblasts are superficial and their presence inversely correlates with wound closure. Expression of TGFβ2 and nuclear localization of pSMAD2 were elevated during myofibroblast induction. BMP3 and BMP7 were localized in the corneal epithelium and corresponded with pSMAD1/5/8 activation and absence of myofibroblasts in the healing stroma. In vitro analyses with corneal fibroblasts revealed that BMP3 inhibits the persistence of TGFβ2-induced myofibroblasts by promoting disassembly of focal adhesions and αSMA fibers. This was confirmed by the expression of vinculin and pFAK. Together, these data highlight a mechanism to inhibit myofibroblast persistence during cornea wound repair.
Bifunctional sulfilimines enable synthesis of multiple N-heterocycles from alkenes
Authors: Cheng Qiang , Bai Zibo , Tewari Srija , Ritter Tobias 
Published: July 2022

AbstractIntramolecular cyclization of nitrogen-containing molecules onto pendant alkenes is an efficient strategy for the construction of N-heterocycles, which are of paramount importance in, for example, pharmaceuticals and materials. Similar intermolecular cyclization reactions, however, are scarcer for nitrogen building blocks, including N-centred radicals, and divergent and modular versions are not established. Here we report the use of sulfilimines as bifunctional N-radical precursors for cyclization reactions with alkenes to produce N-unprotected heterocycles in a single step through photoredox catalysis. Structurally diverse sulfilimines can be synthesized in a single step, and subsequently engage with alkenes to afford synthetically valuable five-, six- and seven-membered heterocycles. The broad and diverse scope is achievable by a radical-polar crossover annulation enabled by the bifunctional character of the reagents, which distinguishes itself from all other N-centred-radical-based reactions. The modular synthesis of the sulfilimines allows for larger structural diversity of N-heterocycle products than is currently achievable with other single cyclization methods.
A crown-group cnidarian from the Ediacaran of Charnwood Forest, UK
Authors: Dunn F. S. , Kenchington C. G. , Parry L. A. , Clark J. W. , Kendall R. S. , Wilby P. R. 
Published: July 2022

AbstractCnidarians are a disparate and ancient phylum, encompassing corals and jellyfish, and occupy both the pelagic and benthic realms. They have a rich fossil record from the Phanerozoic eon lending insight into the early history of the group but, although cnidarians diverged from other animals in the Precambrian period, their record from the Ediacaran period (635–542 million years ago) is controversial. Here, we describe a new fossil cnidarian—Auroralumina attenboroughii gen. et sp. nov.—from the Ediacaran of Charnwood Forest (557–562 million years ago) that shows two bifurcating polyps enclosed in a rigid, polyhedral, organic skeleton with evidence of simple, densely packed tentacles. Auroralumina displays a suite of characters allying it to early medusozoans but shows others more typical of Anthozoa. Phylogenetic analyses recover Auroralumina as a stem-group medusozoan and, therefore, the oldest crown-group cnidarian. Auroralumina demonstrates both the establishment of the crown group of an animal phylum and the fixation of its body plan tens of millions of years before the Cambrian diversification of animal life.
Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei
Authors: López-Escobar Lara , Hänisch Benjamin , Halliday Clare , Ishii Midori , Akiyoshi Bungo , Dean Samuel , Sunter Jack Daniel , Wheeler Richard John , Gull Keith 
Published: July 2022

AbstractVariant surface glycoprotein (VSG) coats bloodstream form Trypanosoma brucei parasites, and monoallelic VSG expression underpins the antigenic variation necessary for pathogenicity. One of thousands of VSG genes is transcribed by RNA polymerase I in a singular nuclear structure called the expression site body (ESB), but how monoallelic VSG transcription is achieved remains unclear. Using a localization screen of 153 proteins we found one, ESB-specific protein 1 (ESB1), that localized only to the ESB and is expressed only in VSG-expressing life cycle stages. ESB1 associates with DNA near the active VSG promoter and is necessary for VSG expression, with overexpression activating inactive VSG promoters. Mechanistically, ESB1 is necessary for recruitment of a subset of ESB components, including RNA polymerase I, revealing that the ESB has separately assembled subdomains. Because many trypanosomatid parasites have divergent ESB1 orthologues yet do not undergo antigenic variation, ESB1 probably represents an important class of transcription regulators.
Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys
Authors: Fenwick Craig , Turelli Priscilla , Ni Dongchun , Perez Laurent , Lau Kelvin , Herate Cécile , Marlin Romain , Lana Erica , Pellaton Céline , Raclot Charlène , Esteves-Leuenberger Line , Campos Jérémy , Farina Alex , Fiscalini Flurin , Dereuddre-Bosquet Nathalie , Relouzat Francis , Abdelnabi Rana , Foo Caroline S. , Neyts Johan , Leyssen Pieter , Lévy Yves , Pojer Florence , Stahlberg Henning , LeGrand Roger , Trono Didier , Pantaleo Giuseppe 
Published: July 2022

AbstractThe SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and is less sensitive to vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from a previously infected vaccinated donor and showed that it has picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other variants tested. We solved the structure of P2G3 Fab in complex with the Omicron spike using cryo-electron microscopy at 3.04 Å resolution to identify the P2G3 epitope as a Class 3 mAb that is different from mAb-binding spike epitopes reported previously. Using a SARS-CoV-2 Omicron monkey challenge model, we show that P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified), confers complete prophylactic or therapeutic protection. Although we could select for SARS-CoV-2 mutants escaping neutralization by P2G3 or by P5C3 in vitro, they had low infectivity and ‘escape’ mutations are extremely rare in public sequence databases. We conclude that this combination of mAbs has potential as an anti-Omicron drug.
Uncovering the mode of action of engineered T cells in patient cancer organoids
Authors: Dekkers Johanna F. , Alieva Maria , Cleven Astrid , Keramati Farid , Wezenaar Amber K. L. , van Vliet Esmée J. , Puschhof Jens , Brazda Peter , Johanna Inez , Meringa Angelo D. , Rebel Heggert G. , Buchholz Maj-Britt , Barrera Román Mario , Zeeman Amber L. , de Blank Sam , Fasci Domenico , Geurts Maarten H. , Cornel Annelisa M. , Driehuis Else , Millen Rosemary , Straetemans Trudy , Nicolasen Mara J. T. , Aarts-Riemens Tineke , Ariese Hendrikus C. R. , Johnson Hannah R. , van Ineveld Ravian L. , Karaiskaki Froso , Kopper Oded , Bar-Ephraim Yotam E. , Kretzschmar Kai , Eggermont Alexander M. M. , Nierkens Stefan , Wehrens Ellen J. , Stunnenberg Henk G. , Clevers Hans , Kuball Jürgen , Sebestyen Zsolt , Rios Anne C. 
Published: July 2022

Abstract
Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics. We apply BEHAV3D to live-track >150,000 engineered T cells cultured with patient-derived, solid-tumor organoids, identifying a ‘super engager’ behavioral cluster comprising T cells with potent serial killing capacity. Among other T cell concepts we also study cancer metabolome-sensing engineered T cells (TEGs) and detect behavior-specific gene signatures that include a group of 27 genes with no previously described T cell function that are expressed by super engager killer TEGs. We further show that type I interferon can prime resistant organoids for TEG-mediated killing. BEHAV3D is a promising tool for the characterization of behavioral-phenotypic heterogeneity of cellular immunotherapies and may support the optimization of personalized solid-tumor-targeting cell therapies.
Prevalence, age of decision, and interpersonal warmth judgements of childfree adults
Authors: Neal Zachary P. , Neal Jennifer Watling 
Published: July 2022

AbstractChildfree adults do not want to have children, making them distinct from parents and other adults without children. However, they are difficult to study because they cannot be identified using conventional data on fertility. We use data from a representative sample in the United States to examine the prevalence, age of decision, and interpersonal warmth judgments by and about childfree adults. Our prevalence estimates suggest that childfree adults are quite common, comprising over one-fifth (21.64%) of the population. Our analysis of age-to-decision suggests that most childfree adults reported that they decided they did not want children early in life. Finally, our analysis of interpersonal warmth suggests asymmetric affective polarization among parents and childfree adults driven primarily by parent’s ingroup favoritism. We discuss the implications of these findings for our understanding of childfree adults and for future research on this historically overlooked segment of the population.
PHARP: a pig haplotype reference panel for genotype imputation
Authors: Wang Zhen , Zhang Zhenyang , Chen Zitao , Sun Jiabao , Cao Caiyun , Wu Fen , Xu Zhong , Zhao Wei , Sun Hao , Guo Longyu , Zhang Zhe , Wang Qishan , Pan Yuchun 
Published: July 2022

AbstractPigs not only function as a major meat source worldwide but also are commonly used as an animal model for studying human complex traits. A large haplotype reference panel has been used to facilitate efficient phasing and imputation of relatively sparse genome-wide microarray chips and low-coverage sequencing data. Using the imputed genotypes in the downstream analysis, such as GWASs, TWASs, eQTL mapping and genomic prediction (GS), is beneficial for obtaining novel findings. However, currently, there is still a lack of publicly available and high-quality pig reference panels with large sample sizes and high diversity, which greatly limits the application of genotype imputation in pigs. In response, we built the pig Haplotype Reference Panel (PHARP) database. PHARP provides a reference panel of 2012 pig haplotypes at 34 million SNPs constructed using whole-genome sequence data from more than 49 studies of 71 pig breeds. It also provides Web-based analytical tools that allow researchers to carry out phasing and imputation consistently and efficiently. PHARP is freely accessible at http://alphaindex.zju.edu.cn/PHARP/index.php. We demonstrate its applicability for pig commercial 50 K SNP arrays, by accurately imputing 2.6 billion genotypes at a concordance rate value of 0.971 in 81 Large White pigs (~ 17 × sequencing coverage). We also applied our reference panel to impute the low-density SNP chip into the high-density data for three GWASs and found novel significantly associated SNPs that might be casual variants.
Repulsive segregation of fluoroalkyl side chains turns a cohesive polymer into a mechanically tough, ultrafast self-healable, nonsticky elastomer
Authors: Miwa Yohei , Udagawa Taro , Kutsumizu Shoichi 
Published: July 2022

AbstractDynamic crosslinking of flexible polymer chains via attractive and reversible interactions is widely employed to obtain autonomously self-healable elastomers. However, this design leads to a trade-off relationship between the strength and self-healing speed of the material, i.e., strong crosslinks provide a mechanically strong elastomer with slow self-healing property. To address this issue, we report an “inversion” concept, in which attractive poly(ethyl acrylate-random-methyl acrylate) chains are dynamically crosslinked via repulsively segregated fluoroalkyl side chains attached along the main chain. The resulting elastomer self-heals rapidly (> 90% within 15 min) via weak but abundant van der Waals interactions among matrix polymers, while the dynamic crosslinking provides high fracture stress (≈2 MPa) and good toughness (≈17 MJ m−3). The elastomer has a nonsticky surface and selectively self-heals only at the damaged faces due to the surface segregation of the fluoroalkyl chains. Moreover, our elastomer strongly adheres to polytetrafluoroethylene plates (≈60 N cm−2) via hot pressing.
Strategies discovery in the active allothetic place avoidance task
Authors: Vouros Avgoustinos , Gehring Tiago V. , Jura Bartosz , Węsierska Małgorzata J. , Wójcik Daniel K. , Vasilaki Eleni 
Published: July 2022

AbstractThe Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.
Spontaneous breathing promotes lung injury in an experimental model of alveolar collapse
Authors: Bachmann María Consuelo , Cruces Pablo , Díaz Franco , Oviedo Vanessa , Goich Mariela , Fuenzalida José , Damiani Luis Felipe , Basoalto Roque , Jalil Yorschua , Carpio David , Hamidi Vadeghani Niki , Cornejo Rodrigo , Rovegno Maximiliano , Bugedo Guillermo , Bruhn Alejandro , Retamal Jaime 
Published: July 2022

AbstractVigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as “patient self-inflicted lung injury”. Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB‐group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late.
Lymphoma total lesion glycolysis leads to hyperlactatemia and reduction of brain glucose utilization
Authors: Yi Hyun Kyung , Yoo Jang , Kim Seok Jin , Choi Joon Young , Lee Kyung-Han 
Published: July 2022

AbstractClarifying the mechanism of lymphoma-associated hyperlactatemia could help identify patients at risk. Here, 129 non-Hodgkin’s lymphoma patients suspected of blood lactate elevation underwent blood measurement and 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) on the same day. Blood lactate elevation was mild (1.0–2.5 mmol/L) in 60, moderate (2.5–4.0 mmol/L) in 46, and severe (≥ 4.0 mmol/L) in 23 subjects. Subjects with severe lactate elevation had higher lymphoma stage, worse IPI risk, poorer ECOG performance, and higher tumor TLG. Furthermore, there was a linear correlation between blood lactate concentration and lymphoma TLG (Spearman’s r = 0.367; P < 0.0001). Brain FDG uptake was low (SUVave < 4.0) in 81 patients that were older, had greater stage and IPI risk, worse ECOG performance, and higher blood lactate. Brain SUVave showed inverse correlation with blood lactate (Spearman’s r = − 0.564; P < 0.0001) and lymphoma TLG (Spearman’s r = − 0.252; P = 0.0066), as well as with stage, ECOG score, and IPI risk. Multivariable regression analysis confirmed increased blood lactate and lymphoma TLG as significant explanatory variables for reduced brain SUVave (both P < 0.0001). Hence, blood lactate elevation in lymphoma patients is the result of glycolytic tumor burden. Since brain cells prefer lactate over glucose as energy source when blood lactate level is increased, this causes proportional reductions of brain FDG uptake. FDG PET/CT can therefore identify high glycolytic lymphoma burden at risk of hyperlactatemia and may provide estimates of its severity by reductions in brain uptake.
Thermal convection in nanofluids for peristaltic flow in a nonuniform channel
Authors: Alhazmi Sharifah E. , Imran Ali , Awais Muhammad , Abbas Mazhar , Alhejaili Weaam , Hamam Haneen , Alhowaity Awatif , Waheed Asif 
Published: July 2022

AbstractA magneto couple stress nanofluid flow along with double diffusive convection is presented for peristaltic induce flow through symmetric nonuniform channel. A comprehensive mathematical model is scrutinized for couple stress nanofluid magneto nanofluids and corresponding equations of motions are tackled by applying small Reynolds and long wavelength approximation in viewing the scenario of the biological flow. Computational solution is exhibited with the help of graphical illustration for nanoparticle volume fraction, solutal concentration and temperature profiles in MATHEMTICA software. Stream function is also computed numerically by utilizing the analytical expression for nanoparticle volume fraction, solutal concentration and temperature profiles. Whereas pressure gradient profiles are investigated analytically. Impact of various crucial flow parameter on the pressure gradient, pressure rise per wavelength, nanoparticle volume fraction, solutal concentration, temperature and the velocity distribution are exhibited graphically. It has been deduced that temperature profile is significantly rise with Brownian motion, thermophoresis, Dufour effect, also it is revealed that velocity distribution really effected with strong magnetic field and with increasing non-uniformity of the micro channel. The information of current investigation will be instrumental in the development of smart magneto-peristaltic pumps in certain thermal and drug delivery phenomenon.
Impact of treatment modalities on prognosis of patients with metastatic renal collecting duct carcinoma
Authors: Qian Xiaoyuan , Wan Junlai , Tan Yuanzhong , Liu Zhenrui , Zhang Ying 
Published: July 2022

AbstractAlthough patients with renal collecting duct carcinoma (CDC) benefit from surgery, the value of cytoreductive nephrectomy (CNx) for the prognosis of patients with metastatic CDC remains unclear. Hence, in this study, we used data from Surveillance, Epidemiology, and End Results (SEER) registry to investigate the prognostic factors and the impact of CNx on the outcomes in patients with metastatic CDC. Data of 521 patients, diagnosed with CDC between 2000 and 2018, were retrieved from the SEER database. Kaplan–Meier method and log-rank tests were used to compare the survival differences between the CNx group and non-surgical group. Multivariate Cox regression analysis was used to identify the risk factors associated with overall survival (OS) and cancer-specific survival (CSS) for patients with metastatic CDC. Moreover, multivariate Cox regression analysis guided by directed acyclic graphs (DAG) was used to unfold the impact of CNx and chemotherapy on OS and CSS. 86 patients were identified to have metastatic CDC. The median OS and CSS time were 5 and 6 months, respectively. The OS rates at 1-, 2- and 5-years were 24.4%, 15.1% and 2.3%, respectively. Whereas, the CSS rates at 1-, 2- and 5-years were 27.0%, 17.9% and 2.8%, respectively. Old patients and those receiving CNx or chemotherapy exhibited better survival outcomes. The multivariate regression model identified non-surgical treatment as the only independent prognostic factor for both, OS and CSS. However, DAG-guided multivariate Cox regression model showed that both, CNx and chemotherapy, were associated with both, OS and CSS. Patients with metastatic CDC exhibited worse clinical outcomes. However, CNx improved the prognosis of patients with metastatic CDC. Additionally, surgical resection of visible lesions and suitable chemotherapy were identified as alternative treatment strategies.