bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetorotational core-collapse supernovae: the impact of the magnetic field’s structure
Authors: Bugli Matteo , Guilet Jérôme , Obergaulinger Martin
Published: February 2023

The combination of strong magnetic fields and fast rotation is often invoked as a characteristic of the central engine for outstanding sources such as GRBs, hypernovae, and superluminous supernovae. However, the actual properties of the magnetic field during the collapse of the stellar progenitor are very uncertain, since they depend on the evolution of the star and can be affected by complex dynamo processes occurring in the central proto-neutron star. Using 3D relativistic MHD models we show that higher-order multipolar fields can lead to the onset of a supernova, although they tend to produce less energetic explosions and less collimated outflows. Quadrupolar fields efficiently extract angular momentum from the central core, but the rotational energy is partly stored in the equatorial regions, rather than powering up the polar outflows. Finally, our results show a strong magnetic quenching of the hydrodynamic non-axisymmetric instabilities that are associated to the emission of GWs.
Observations of Gravitational-wave Afterglows
Authors: Corsi Alessandra
Published: February 2023

GW170817, the merger of two neutron stars witnessed through both its gravitational wave siren and its glow at all wavelengths of light, represents the first multi-messenger detection of a compact binary merger. The association of the GW in-spiral signal from GW170817 with a γ-ray burst, a kilonova, and a non-thermal afterglow spanning all bands of the electromagnetic spectrum, has provided rich constraints on the physics and astrophysics of neutron stars. Starting from the example of GW170817, I briefly summarize recent results on observations of electromagnetic afterglows from gravitational wave triggers. In the light of these results, I highlight some key questions that are yet to be answered after the GW170817 discovery. I conclude by commenting briefly on some opportunities that lie in front of us, as improvements in ground-based gravitational wave detectors’ sensitivities will transform a trickle of multi-messenger discoveries into a flood, bringing the field of gravitational wave astronomy from its infancy to its maturity.
GRB 170817A and the long-term aftermath of neutron star mergers
Authors: van Eerten Hendrik
Published: February 2023

GW170817/GRB 170817A has had a huge impact on our understanding of gamma-ray burst (GRB) afterglows, and has prompted a huge sustained effort at modeling the details of the geometry and emission from GRB jets. While no additional electro-magnetic counterparts have been detected to gravitational wave emission from neutron star mergers so far, it is certainly reasonable to expect further detections in the future. Whether these will be very similar in nature to GRB 170817A or instead will provide us with samplings of afterglow model parameters across a wide parameter space remains an open question. In this presentation I will survey some of the work done by the various active groups worldwide in theoretical modeling and understanding afterglows post 170817A.
HARM3D+NUC: GRMHD, nuclear tables and neutrino leakage
Authors: Murguia-Berthier Ariadna , Noble Scott C. , Roberts Luke F. , Ramirez-Ruiz Enrico
Published: February 2023

On August 17, 2017, the LIGO/VIRGO collaboration detected the first gravitational wave signal coming from the merger of two neutron stars. This groundbreaking discovery, referred to as GW170817, revealed to us how heavy elements, such as gold and platinum, are synthesized through a mechanism known as rapid neutron capture (r-process). In order to fully understand these signals, we need to simulate the resulting accretion disk around a black hole, and its outflows. This task requires efficient computing codes that include general relativity magnetohydrodynamics (GRMHD), neutrino physics, and a model for matter at high densities. We present the implementation of a tabulated equation of state that takes care of matter at high densities and a neutrino leakage scheme that considers the impact of neutrinos into HARM3D, a GRMHD parallelized code. We also apply the tools to a magnetized torus.
THE ZHOU ORDINAL OF LABELLED MARKOV PROCESSES OVER SEPARABLE SPACES
Authors: MORONI MARTÍN SANTIAGO , SÁNCHEZ TERRAF PEDRO
Published: February 2023

There exist two notions of equivalence of behavior between states of a Labelled Markov Process (LMP): state bisimilarity and event bisimilarity. The first one can be considered as an appropriate generalization to continuous spaces of Larsen and Skou’s probabilistic bisimilarity, whereas the second one is characterized by a natural logic. C. Zhou expressed state bisimilarity as the greatest fixed point of an operator
$\mathcal {O}$
, and thus introduced an ordinal measure of the discrepancy between it and event bisimilarity. We call this ordinal the Zhou ordinal of
$\mathbb {S}$
,
$\mathfrak {Z}(\mathbb {S})$
. When
$\mathfrak {Z}(\mathbb {S})=0$
,
$\mathbb {S}$
satisfies the Hennessy–Milner property. The second author proved the existence of an LMP
$\mathbb {S}$
with
$\mathfrak {Z}(\mathbb {S}) \geq 1$
and Zhou showed that there are LMPs having an infinite Zhou ordinal. In this paper we show that there are LMPs
$\mathbb {S}$
over separable metrizable spaces having arbitrary large countable
$\mathfrak {Z}(\mathbb {S})$
and that it is consistent with the axioms of
$\mathit {ZFC}$
that there is such a process with an uncountable Zhou ordinal.
AXIOMS FOR TYPE-FREE SUBJECTIVE PROBABILITY
Authors: CIEŚLIŃSKI CEZARY , HORSTEN LEON , LEITGEB HANNES
Published: February 2023

We formulate and explore two basic axiomatic systems of type-free subjective probability. One of them explicates a notion of finitely additive probability. The other explicates a concept of infinitely additive probability. It is argued that the first of these systems is a suitable background theory for formally investigating controversial principles about type-free subjective probability.
Characteristics of Electron Precipitation Directly Driven by Poloidal ULF Waves
Authors: Yin Ze‐Fan , Zhou Xu‐Zhi , Li Wen , Shen Xiao‐Chen , Rankin Robert , Liu Ji , Hu Ze‐Jun , Liu Jian‐Jun , Zong Qiu‐Gang , Li Li , Wang Yong‐Fu
Published: February 2023

A mechanism recently proposed for magnetospheric electron loss into the atmosphere is the precipitation directly driven by ultralow‐frequency (ULF) waves. In this study, we quantitatively analyze the properties of ULF wave‐induced precipitation by simulating the electron bounce and drift motion in poloidal‐mode waves excited in a dipole magnetic field. Our results reveal that precipitation occurs only when electrons encounter a westward‐directed wave electric field in the magnetosphere, which leads to cross‐field energy enhancements and reduces their mirror heights. The simulations also demonstrate longer duration electron precipitation at the drift‐resonance energy. We calculate the temporal variations of the energy spectrum for precipitating electrons and the total precipitating energy fluxes. These results improve our understanding of ULF wave‐induced electron precipitation as well as provide a point of comparison for observations from balloons or ground‐based instruments.
A New P‐Wave Tomographic Model (CAP22) for North America: Implications for the Subduction and Cratonic Metasomatic Modification History of Western Canada and Alaska
Authors: Boyce A. , Liddell M. V. , Pugh S. , Brown J. , McMurchie E. , Parsons A. , Estève C. , Burdick S. , Darbyshire F. A. , Cottaar S. , Bastow I. D. , Schaeffer A. J. , Audet P. , Schutt D. L. , Aster R. C.
Published: February 2023

Our understanding of the present‐day state and evolution of the Canadian and Alaskan mantle is hindered by a lack of absolute P‐wavespeed constraints that provide complementary sensitivity to composition in conjunction with existing S‐wavespeed models. Consequently, cratonic modification, orogenic history of western North America and complexities within the Alaskan Proto‐Pacific subduction system remain enigmatic. One challenge concerns the difficulties in extracting absolute arrival‐time measurements from often‐noisy data recorded by temporary seismograph networks required to fill gaps in continental and global databases. Using the Absolute Arrival‐time Recovery Method (AARM), we extract >180,000 new absolute arrival‐time residuals from seismograph stations across Canada and Alaska and combine these data with USArray and global arrival‐time data from the contiguous US and Alaska. We develop a new absolute P‐wavespeed tomographic model, CAP22, spanning North America that significantly improves resolution in Canada and Alaska over previous models. Slow wavespeeds below the Canadian Cordillera sharply abut fast wavespeeds of the continental interior at the Rocky Mountain Trench in southwest Canada. Slow wavespeeds below the Mackenzie Mountains continue farther inland in northwest Canada, indicating Proterozoic‐Archean metasomatism of the Slave craton. Inherited tectonic lineaments colocated with this north‐south wavespeed boundary suggest that both the crust and mantle may control Cordilleran orogenic processes. In Alaska, fast upper mantle wavespeeds below the Wrangell Volcanic Field favor a conventional subduction related mechanism for volcanism. Finally, seismic evidence for the subducted Kula and Yukon slabs indicate tectonic reconstructions of western North America may require revision.
Tracking a Pyroclastic Density Current With Seismic Signals at Mt. Etna (Italy)
Authors: Watson Leighton M. , Cannata Andrea , Andronico Daniele
Published: February 2023

Pyroclastic density currents (PDCs) are dangerous flows of volcanic rock and gas that are the most deadly proximal volcano hazard. There is significant interest in better understanding PDC dynamics, however, they are challenging to study due to their extreme hazard, unpredictable occurrence, and because complex internal dynamics are obscured by visually opaque clouds of ash. PDCs exert forces on Earth's surface and generate seismic waves. Here, we use seismic data recorded by the permanent monitoring network at Mt. Etna (Italy) to track the 11 February 2014 PDC at second‐scale temporal resolution and calculate a maximum velocity of 76 m/s (274 km/hr). We identify multiple pulses and show that the late‐stage source locations correspond with the mapped coarse‐grained PDC deposits. High temporal and spatial resolution measurements of PDC movement from seismic data can be used to inform numerical modeling of PDC dynamics and aid in hazard assessment by improving our understanding of PDC flow paths. This work illustrates how seismic signals can be used to track surficial mass movements in real‐time.
Machine Learning of Key Variables Impacting Extreme Precipitation in Various Regions of the Contiguous United States
Authors: Lin Xinming , Fan Jiwen , Hou Z. Jason , Wang Jingyu
Published: February 2023

Amplification in extreme precipitation intensity and frequency can cause severe flooding and impose significant social and economic consequences. Variations in extreme precipitation intensity, frequencies, and return periods can be attributed to many physical variables across spatial and temporal scales. Here we employ ensemble machine learning (ML) methods, namely random forest (RF), eXtreme Gradient Boosting (XGB), and artificial neural networks (ANN), to explore key contributing variables to monthly extreme precipitation intensity and frequency in six regions over the United States. We further establish emulators for return periods. Results show that the ML models for intensity perform better in regions with obvious seasonality (i.e., Northern Great Plains, Southern Great Plains, and West Coast) than the other three regions (Northeast, Southwest, and Rocky Mountains), while for frequency the models perform well for most regions. The Shapley additive explanation is used to help explain the relationships between extreme precipitation characteristics and identify top variables for RF and XGB. We find that latent heat flux, relative humidity, soil moisture, and large‐scale subsidence are key common variables across the regions for both monthly intensity and frequency, and their compound effects are non‐negligible. The developed ML models capture the probability and return period of extreme precipitation well for all regions and may be used for decision making (e.g., infrastructure planning and design).
Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation
Authors: Guirado Elizabeth , Villani Cassandra , Petho Adrienn , Chen Yinghua , Maienschein-Cline Mark , Lei Zhengdeng , Los Nina , George Anne
Published: February 2023

X-linked hypophosphatemia (XLH) represents the most common form of familial hypophosphatemia. Although significant advances have been made in the treatment of bone pathology, patients undergoing therapy continue to experience significantly decreased oral health-related quality of life. The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells. Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved. RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation. RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells, while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation. These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.
Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy
Authors: Moscvin Maria , Liacos Christine Ivy , Chen Tianzeng , Theodorakakou Foteini , Fotiou Despina , Hossain Shahrier , Rowell Sean , Leblebjian Houry , Regan Eileen , Czarnecki Peter , Bagnoli Filippo , Bolli Niccolo’ , Richardson Paul , Rennke Helmut G. , Dimopoulos Meletios A. , Kastritis Efstathios , Bianchi Giada
Published: February 2023

Thrombotic microangiopathy (TMA) has been reported to occur in multiple myeloma (MM) patients in association with treatment with carfilzomib, an irreversible proteasome inhibitor (PI). The hallmark of TMA is vascular endothelial damage leading to microangiopathic hemolytic anemia, platelet consumption, fibrin deposition and small-vessel thrombosis with resultant tissue ischemia. The molecular mechanisms underlying carfilzomib-associated TMA are not known. Germline mutations in the complement alternative pathway have been recently shown to portend increased risk for the development of atypical hemolytic uremic syndrome (aHUS) and TMA in the setting of allogeneic stem cell transplant in pediatric patients. We hypothesized that germline mutations in the complement alternative pathway may similarly predispose MM patients to carfilzomib-associated TMA. We identified 10 MM patients with a clinical diagnosis of TMA in the context of carfilzomib treatment and assessed for the presence of germline mutations in the complement alternative pathway. Ten, matched MM patients exposed to carfilzomib but without clinical TMA were used as negative controls. We identified a frequency of deletions in the complement Factor H genes 3 and 1 (delCFHR3-CFHR1) and genes 1 and 4 (delCFHR1-CFHR4) in MM patients with carfilzomib-associated TMA that was higher as compared to the general population and matched controls. Our data suggest that complement alternative pathway dysregulation may confer susceptibility to vascular endothelial injury in MM patients and predispose to development of carfilzomib-associated TMA. Larger, retrospective studies are needed to evaluate whether screening for complement mutations may be indicated to properly counsel patients about TMA risk with carfilzomib use.
Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy
Authors: Chemello Francesco , Pozzobon Michela , Tsansizi Lorenza Iolanda , Varanita Tatiana , Quintana-Cabrera Rubèn , Bonesso Daniele , Piccoli Martina , Lanfranchi Gerolamo , Giacomello Marta , Scorrano Luca , Bean Camilla
Published: February 2023

The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy.
The MYC-regulated lncRNA LNROP (ENSG00000254887) enables MYC-driven cell proliferation by controlling the expression of OCT2
Authors: García-Caballero Daniel , Hart Jonathan R. , Vogt Peter K.
Published: February 2023

MYC controls most of the non-coding genome. Several long noncoding transcripts were originally identified in the human B cell line P496-3 and then shown to be required for MYC-driven proliferation of Burkitt lymphoma-derived RAMOS cells. In this study, we used RAMOS cells exclusively as a representative of the human B cell lineage. One of the MYC-controlled lncRNAs required for RAMOS cell proliferation is ENSG00000254887 which we will term LNROP (long non-coding regulator of POU2F2). In the genome, LNROP is located in close proximity of POU2F2, the gene encoding OCT2. OCT2 is a transcription factor with important roles in sustaining the proliferation of human B cells. Here we show that LNROP is a nuclear RNA and a direct target of MYC. Downregulation of LNROP attenuates the expression of OCT2. This effect of LNROP on the expression of OCT2 is unidirectional as downregulation of OCT2 does not alter the expression of LNROP. Our data suggest that LNROP is a cis-acting regulator of OCT2. To illustrate the downstream reach of LNROP, we chose a prominent target of OCT2, the tyrosine phosphatase SHP-1. Downregulation of OCT2 elevates the expression of SHP-1. Our data suggest the following path of interactions: LNROP enables the proliferation of B cells by positively and unidirectionally regulating the growth-stimulatory transcription factor OCT2. In actively proliferating B cells, OCT2 attenuates the expression and anti-proliferative activity of SHP-1.
The UDPase ENTPD5 regulates ER stress-associated renal injury by mediating protein N-glycosylation
Authors: Xu Lifen , Zhou Yuxia , Wang Guifang , Bo Li , Jin Bangming , Dai Lujun , Lu Qinli , Cai Xueni , Hu Laying , Liu Lu , Wu Yixuan , Chang Xuebing , Huang Yali , Song Lingyu , Zhang Tian , Wang Yuanyuan , Xiao Ying , Zhang Fan , Liu Lingling , Shi Mingjun , Wang Tuanlao , Guo Bing
Published: February 2023

Impaired protein N-glycosylation leads to the endoplasmic reticulum (ER) stress, which triggers adaptive survival or maladaptive apoptosis in renal tubules in diabetic kidney disease (DKD). Therapeutic strategies targeting ER stress are promising for the treatment of DKD. Here, we report a previously unappreciated role played by ENTPD5 in alleviating renal injury by mediating ER stress. We found that ENTPD5 was highly expressed in normal renal tubules; however, ENTPD5 was dynamically expressed in the kidney and closely related to pathological DKD progression in both human patients and mouse models. Overexpression of ENTPD5 relieved ER stress in renal tubular cells, leading to compensatory cell proliferation that resulted in hypertrophy, while ENTPD5 knockdown aggravated ER stress to induce cell apoptosis, leading to renal tubular atrophy and interstitial fibrosis. Mechanistically, ENTPD5-regulated N-glycosylation of proteins in the ER to promote cell proliferation in the early stage of DKD, and continuous hyperglycemia activated the hexosamine biosynthesis pathway (HBP) to increase the level of UDP-GlcNAc, which driving a feedback mechanism that inhibited transcription factor SP1 activity to downregulate ENTPD5 expression in the late stage of DKD. This study was the first to demonstrate that ENTPD5 regulated renal tubule cell numbers through adaptive proliferation or apoptosis in the kidney by modulating the protein N-glycosylation rate in the ER, suggesting that ENTPD5 drives cell fate in response to metabolic stress and is a potential therapeutic target for renal diseases.
Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors
Authors: Isoyama Sho , Tamaki Naomi , Noguchi Yutaka , Okamura Mutsumi , Yoshimatsu Yuki , Kondo Tadashi , Suzuki Takeshi , Yaguchi Shin-ichi , Dan Shingo
Published: February 2023

Translocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have yet to be established. We previously reported that a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, ZSTK474, was effective for the treatment of sarcomas in a phase I clinical trial. We also demonstrated the efficacy of ZSTK474 in a preclinical model, particularly in cell lines from synovial sarcoma (SS), Ewing’s sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS), all of which harbor chromosomal translocations. ZSTK474 selectively induced apoptosis in all these sarcoma cell lines, although the precise mechanism underlying the induction of apoptosis remained unclear. In the present study, we aimed to determine the antitumor effect of PI3K inhibitors, particularly with regards to the induction of apoptosis, against various TRS subtypes using cell lines and patient-derived cells (PDCs). All of the cell lines derived from SS (six), ES (two) and ARMS (one) underwent apoptosis accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP) and the loss of mitochondrial membrane potential. We also observed apoptotic progression in PDCs from SS, ES and clear cell sarcoma (CCS). Transcriptional analyses revealed that PI3K inhibitors triggered the induction of PUMA and BIM and the knockdown of these genes by RNA interference efficiently suppressed apoptosis, suggesting their functional involvement in the progression of apoptosis. In contrast, TRS-derived cell lines/PDCs from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. Thus, we conclude that PI3K inhibitors induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and the subsequent loss of mitochondrial membrane potential. This represents proof of concept for PI3K-targeted therapy, particularly such TRS patients.
The double-edged functions of necroptosis
Authors: Ye Keng , Chen Zhimin , Xu Yanfang
Published: February 2023

Necroptosis refers to a regulated form of cell death induced by a variety of stimuli. Although it has been implicated in the pathogenesis of many diseases, there is evidence to support that necroptosis is not purely a detrimental process. We propose that necroptosis is a “double-edged sword” in terms of physiology and pathology. On the one hand, necroptosis can trigger an uncontrolled inflammatory cascade response, resulting in severe tissue injury, disease chronicity, and even tumor progression. On the other hand, necroptosis functions as a host defense mechanism, exerting antipathogenic and antitumor effects through its powerful pro-inflammatory properties. Moreover, necroptosis plays an important role during both development and regeneration. Misestimation of the multifaceted features of necroptosis may influence the development of therapeutic approaches targeting necroptosis. In this review, we summarize current knowledge of the pathways involved in necroptosis as well as five important steps that determine its occurrence. The dual role of necroptosis in a variety of physiological and pathological conditions is also highlighted. Future studies and the development of therapeutic strategies targeting necroptosis should fully consider the complicated properties of this type of regulated cell death.
Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming
Authors: Aso Kuniyuki , Kono Michihito , Kanda Masatoshi , Kudo Yuki , Sakiyama Kodai , Hisada Ryo , Karino Kohei , Ueda Yusho , Nakazawa Daigo , Fujieda Yuichiro , Kato Masaru , Amengual Olga , Atsumi Tatsuya
Published: February 2023

Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased RORγt binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.
Red light-driven electron sacrificial agents-free photoreduction of inert aryl halides via triplet-triplet annihilation
Authors: Zeng Le , Huang Ling , Lin Wenhai , Jiang Lin-Han , Han Gang
Published: February 2023

Selective photoactivation of inert aryl halides is a fundamental challenge in organic synthesis. Specially, the long-wavelength red light is more desirable than the widely-applied blue light as the excitation source for photoredox catalysis, due to its superior penetration depth. However, the long-wavelength red light-driven photoactivation of inert aryl halides remains a challenge, mainly because of the low energy of the single long-wavelength red photon. Herein, we report the photoreduction of aryl bromides/chlorides with 656 nm LED via triplet-triplet annihilation (TTA) strategy. This method is based on our discovery that the commonly used chromophore of perylene can serve as an efficient and metal-free photocatalyst to enable the photoreduction of inert aryl halides without the conventional need for electronic sacrificial agents. By introducing a red light-absorbing photosensitizer to this perylene system, we accomplish the long-wavelength red light-driven photoreduction of aryl halides via sensitized TTA mechanism. Moreover, the performance of such a TTA-mediated photoreduction can be significantly enhanced when restricting the rotation freedom of phenyl moiety for perylene derivatives to suppress their triplet nonradiative transition, in both small and large-scale reaction settings.
Noncanonical electromechanical coupling paths in cardiac hERG potassium channel
Authors: Bassetto Carlos A. Z. , Costa Flavio , Guardiani Carlo , Bezanilla Francisco , Giacomello Alberto
Published: February 2023

Voltage-gated potassium channels are involved in many physiological processes such as nerve impulse transmission, the heartbeat, and muscle contraction. However, for many of them the molecular determinants of the gating mechanism remain elusive. Here, using a combination of theoretical and experimental approaches, we address this problem focusing on the cardiac hERG potassium channel. Network analysis of molecular dynamics trajectories reveals the presence of a kinematic chain of residues that couples the voltage sensor domain to the pore domain and involves the S4/S1 and S1/S5 subunit interfaces. Mutagenesis experiments confirm the role of these residues and interfaces in the activation and inactivation mechanisms. Our findings demonstrate the presence of an electromechanical transduction path crucial for the non-domain-swapped hERG channel gating that resembles the noncanonical path identified in domain-swapped K+channels.
Polyfunctionalization of vicinal carbon centers and synthesis of unsymmetric 1,2,3,4-tetracarbonyl compounds
Authors: De Angelis Luca , Pei Chao , Narro Ana L. , Wherritt Daniel , Koenigs Rene M. , Doyle Michael P.
Published: February 2023

The synthesis and characterization of organic compounds with unusual atom or functional group connectivity is one of the main driving forces in the discovery of new synthetic methods that has raised the interest of chemists for many years. Polycarbonyl compounds are such compounds wherein multiple carbonyl groups are directly juxtaposed and influence each other’s chemical reactivity. While 1,2-dicarbonyl or 1,2,3-tricarbonyl compounds are well-known in organic chemistry, the 1,2,3,4-tetracarbonyl motif remains barely explored. Herein, we report on the synthesis of such 1,2,3,4-tetracarbonyl compounds employing a synthetic strategy that involves C-nitrosation of enoldiazoacetates, while the diazo functional group remains untouched. This strategy not only leverages the synthesis of 1,2,3,4-tetracarbonyl compounds to an unprecedented level, it also accomplishes the synthesis of 1,2,3,4-tetracarbonyl compounds, wherein each carbonyl group is orthogonally masked. Combined experimental and theoretical studies provide an understanding of the reaction mechanism and rationalize the formation of such 1,2,3,4-tetracarbonyl compounds.
Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes
Authors: Dufour Caroline , Richard Corentin , Pardons Marion , Massanella Marta , Ackaoui Antoine , Murrell Ben , Routy Bertrand , Thomas Réjean , Routy Jean-Pierre , Fromentin Rémi , Chomont Nicolas
Published: February 2023

The phenotype of the rare HIV-infected cells persisting during antiretroviral therapies (ART) remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses to characterize the viral reservoir in 6 male individuals on suppressive ART. We show that individual cells carrying clonally expanded identical proviruses display very diverse phenotypes, indicating that cellular proliferation contributes to the phenotypic diversification of the HIV reservoir. Unlike most viral genomes persisting on ART, inducible and translation-competent proviruses rarely present large deletions but are enriched in defects in the Ψ locus. Interestingly, the few cells harboring genetically intact and inducible viral genomes express higher levels of the integrin VLA-4 compared to uninfected cells or cells with defective proviruses. Viral outgrowth assay confirmed that memory CD4+ T cells expressing high levels of VLA-4 are highly enriched in replication-competent HIV (27-fold enrichment). We conclude that although clonal expansions diversify the phenotype of HIV reservoir cells, CD4+ T cells harboring replication-competent HIV retain VLA-4 expression.
Room-temperature photosynthesis of propane from CO2 with Cu single atoms on vacancy-rich TiO2
Authors: Shen Yan , Ren Chunjin , Zheng Lirong , Xu Xiaoyong , Long Ran , Zhang Wenqing , Yang Yong , Zhang Yongcai , Yao Yingfang , Chi Haoqiang , Wang Jinlan , Shen Qing , Xiong Yujie , Zou Zhigang , Zhou Yong
Published: February 2023

Photochemical conversion of CO2 into high-value C2+ products is difficult to achieve due to the energetic and mechanistic challenges in forming multiple C-C bonds. Herein, an efficient photocatalyst for the conversion of CO2 into C3H8 is prepared by implanting Cu single atoms on Ti0.91O2 atomically-thin single layers. Cu single atoms promote the formation of neighbouring oxygen vacancies (VOs) in Ti0.91O2 matrix. These oxygen vacancies modulate the electronic coupling interaction between Cu atoms and adjacent Ti atoms to form a unique Cu-Ti-VO unit in Ti0.91O2 matrix. A high electron-based selectivity of 64.8% for C3H8 (product-based selectivity of 32.4%), and 86.2% for total C2+ hydrocarbons (product-based selectivity of 50.2%) are achieved. Theoretical calculations suggest that Cu-Ti-VO unit may stabilize the key *CHOCO and *CH2OCOCO intermediates and reduce their energy levels, tuning both C1-C1 and C1-C2 couplings into thermodynamically-favourable exothermal processes. Tandem catalysis mechanism and potential reaction pathway are tentatively proposed for C3H8 formation, involving an overall (20e− – 20H+) reduction and coupling of three CO2 molecules at room temperature.
Thermodynamics of diamond formation from hydrocarbon mixtures in planets
Authors: Cheng Bingqing , Hamel Sebastien , Bethkenhagen Mandy
Published: February 2023

Hydrocarbon mixtures are extremely abundant in the Universe, and diamond formation from them can play a crucial role in shaping the interior structure and evolution of planets. With first-principles accuracy, we first estimate the melting line of diamond, and then reveal the nature of chemical bonding in hydrocarbons at extreme conditions. We finally establish the pressure-temperature phase boundary where it is thermodynamically possible for diamond to form from hydrocarbon mixtures with different atomic fractions of carbon. Notably, here we show a depletion zone at pressures above 200 GPa and temperatures below 3000 K-3500 K where diamond formation is thermodynamically favorable regardless of the carbon atomic fraction, due to a phase separation mechanism. The cooler condition of the interior of Neptune compared to Uranus means that the former is much more likely to contain the depletion zone. Our findings can help explain the dichotomy of the two ice giants manifested by the low luminosity of Uranus, and lead to a better understanding of (exo-)planetary formation and evolution.
Metasurface-stabilized optical microcavities
Authors: Ossiander Marcus , Meretska Maryna Leonidivna , Rourke Sarah , Spägele Christina , Yin Xinghui , Benea-Chelmus Ileana-Cristina , Capasso Federico
Published: February 2023

Cavities concentrate light and enhance its interaction with matter. Confining to microscopic volumes is necessary for many applications but space constraints in such cavities limit the design freedom. Here we demonstrate stable optical microcavities by counteracting the phase evolution of the cavity modes using an amorphous Silicon metasurface as cavity end mirror. Careful design allows us to limit the metasurface scattering losses at telecom wavelengths to less than 2% and using a distributed Bragg reflector as metasurface substrate ensures high reflectivity. Our demonstration experimentally achieves telecom-wavelength microcavities with quality factors of up to 4600, spectral resonance linewidths below 0.4 nm, and mode volumes below $$2.7{\lambda }^{3}$$
2.7

λ

3

. The method introduces freedom to stabilize modes with arbitrary transverse intensity profiles and to design cavity-enhanced hologram modes. Our approach introduces the nanoscopic light control capabilities of dielectric metasurfaces to cavity electrodynamics and is industrially scalable using semiconductor manufacturing processes.
Using machine learning with optical profilometry for GaN wafer screening
Authors: Gallagher James C. , Mastro Michael A. , Ebrish Mona A. , Jacobs Alan G. , Gunning Brendan P. , Kaplar Robert J. , Hobart Karl D. , Anderson Travis J.
Published: February 2023

To improve the manufacturing process of GaN wafers, inexpensive wafer screening techniques are required to both provide feedback to the manufacturing process and prevent fabrication on low quality or defective wafers, thus reducing costs resulting from wasted processing effort. Many of the wafer scale characterization techniques—including optical profilometry—produce difficult to interpret results, while models using classical programming techniques require laborious translation of the human-generated data interpretation methodology. Alternatively, machine learning techniques are effective at producing such models if sufficient data is available. For this research project, we fabricated over 6000 vertical PiN GaN diodes across 10 wafers. Using low resolution wafer scale optical profilometry data taken before fabrication, we successfully trained four different machine learning models. All models predict device pass and fail with 70–75% accuracy, and the wafer yield can be predicted within 15% error on the majority of wafers.
Modulation of amygdala activity for emotional faces due to botulinum toxin type A injections that prevent frowning
Authors: Stark Shauna , Stark Craig , Wong Brian , Brin Mitchell F.
Published: February 2023

According to the facial feedback hypothesis, when we see an angry or happy face, we contract or flex the relevant muscles to recreate the expression to assist in identifying and experiencing the emotion reflected. We investigated the facial feedback hypothesis by using botulinum toxin type A (onabotulinumtoxinA; onabotA) injections to induce temporary paralysis in the glabellar muscles (responsible for frowning) and measured functional brain activity during the processing of emotional faces. Ten females viewed pictures of happy and angry faces during two functional magnetic resonance imaging (fMRI) scan sessions: one prior (Pre) to onabotA and one following (Active) onabotA injections. We found Pre vs. Active onabotA modulation of activity in the amygdala for both happy and angry faces, as well as modulation of activity in the fusiform gyrus for happy faces. Consistent with our predictions, preventing frowning through inhibition of glabellar muscle contraction altered amygdala processing for emotional faces. The modulation of amygdala and fusiform gyrus activity following onabotA may reflect compensatory processes in a neuroanatomical circuit involved in emotional processing that is engaged when facial feedback is impaired. These data contribute to a growing literature suggesting that inhibition of glabellar muscle contraction alters neural activity for emotional processing.

Clinical Trials.gov registration number: NCT03373162.
Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture
Authors: Dvinskikh L. , Sparks H. , Brito L. , MacLeod K. T. , Harding S. E. , Dunsby C.
Published: February 2023

Improving cardiac function through stem-cell regenerative therapy requires functional and structural integration of the transplanted cells with the host tissue. Visualizing the electromechanical interaction between native and graft cells necessitates 3D imaging with high spatio-temporal resolution and low photo-toxicity. A custom light-sheet fluorescence microscope was used for volumetric imaging of calcium dynamics in co-cultures of adult rat left ventricle cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes. Aberration-free remote refocus of the detection plane synchronously to the scanning of the light sheet along the detection axis enabled fast dual-channel 3D imaging at subcellular resolution without mechanical sample disturbance at up to 8 Hz over a ∼300 µm × 40 µm × 50 µm volume. The two cell types were found to undergo electrically stimulated and spontaneous synchronized calcium transients and contraction. Electromechanical coupling improved with co-culture duration, with 50% of adult-CM coupled after 24 h of co-culture, compared to 19% after 4 h (p = 0.0305). Immobilization with para-nitroblebbistatin did not prevent calcium transient synchronization, with 35% and 36% adult-CM coupled in control and treated samples respectively (p = 0.91), indicating that electrical coupling can be maintained independently of mechanotransduction.
Fragmentation and correlations in a rotating Bose–Einstein condensate undergoing breakup
Authors: Dutta Sunayana , Lode Axel U. J. , Alon Ofir E.
Published: February 2023

The theoretical investigation of rotating Bose–Einstein condensates has mainly focused on the emergence of quantum vortex states and the condensed properties of such systems. In the present work, we concentrate on other facets by examining the impact of rotation on the ground state of weakly interacting bosons confined in anharmonic potentials computed both at the mean-field level and particularly at the many-body level of theory. For the many-body computations, we employ the well-established many-body method known as the multiconfigurational time-dependent Hartree method for bosons. We present how various degrees of fragmentation can be generated following the breakup of the ground state densities in anharmonic traps without ramping up a potential barrier for strong rotations. The breakup of the densities is found to be associated with the acquisition of angular momentum in the condensate due to the rotation. In addition to fragmentation, the presence of many-body correlations is examined by computing the variances of the many-particle position and momentum operators. For strong rotations, the many-body variances become smaller than their mean-field counterparts, and one even finds a scenario with opposite anisotropies of the mean-field and many-body variances. Further, it is observed that for higher discrete symmetric systems of order k, namely three-fold and four-fold symmetry, breakup to k sub-clouds and emergence of k-fold fragmentation take place. All in all, we provide a thorough many-body investigation of how and which correlations build up when a trapped Bose–Einstein condensate breaks up under rotation.
Disentangling the personality pathways to well-being
Authors: Moreira Paulo A. S. , Inman Richard A. , Cloninger C. Robert
Published: February 2023

Recent genomic, psychological, and developmental research shows that human personality is organized as a complex hierarchy that ascends from individual traits in many specific situations to multi-trait profiles in two domains that regulate emotional reactivity (temperament) or goals and values (character), and finally to three integrated temperament-character networks that regulate learning to maintain well-being in changing conditions. We carried out person-centered analyses of the components of subjective well-being (positive affect, negative affect, and life satisfaction) to personality in both adolescents (N = 1739) and adults (N = 897). Personality was considered at each level of its organization (trait, temperament or character profiles, and joint temperament-character networks). We show for the first time that negative affect and life satisfaction are dependent on the personality network for intentional self-control, whereas positive affect is dependent on the personality network for self-awareness that underlies the human capacities for healthy longevity, creativity, and prosocial values.
Risk perception and gratitude mediate the negative relationship between COVID-19 management satisfaction and public anxiety
Authors: Mei Ying , Tan Lisha , Yang Wenmin , Luo Jie , Xu Lei , Lei Yi , Li Hong
Published: February 2023

In this study, we explored whether satisfaction with government management, perception of risk, and gratitude influenced public anxiety during the COVID-19 pandemic in China. Using a cross-sectional, anonymous and confidential online survey, a nationwide sample of Chinese adults (N = 876) was targeted between March 25–March 30, 2020, a period in which newly confirmed cases significantly declined in China. The anxiety level was decreased as compared to that assessed during the peak period. Multiple parallel mediation modeling demonstrated that risk perception and gratitude partially mediated the relationship between satisfaction with government management and public anxiety. Increasing satisfaction and gratitude, as well as reducing risk perception contribute to the public’s mental health. The results may shed light on the positive factors for psychological well-being during the COVID-19 pandemic and may aid potential strategies for the policy maker, the public, and the clinic to regulate negative emotions or future emerging infectious diseases.
Delta (B1.617.2) variant of SARS-CoV-2 induces severe neurotropic patterns in K18-hACE2 mice
Authors: Yang Ju-Hee , Yang Myeon-Sik , Kim Dae-Min , Kim Bumseok , Tark Dongseob , Kang Sang-Min , Lee Gun-Hee
Published: February 2023

A highly contagious virus, severe acute respiratory syndrome coronavirus 2, caused the coronavirus disease 19 (COVID-19) pandemic (SARS-CoV-2). SARS-CoV-2 genetic variants have been reported to circulate throughout the COVID-19 pandemic. COVID-19 symptoms include respiratory symptoms, fever, muscle pain, and breathing difficulty. In addition, up to 30% of COVID-19 patients experience neurological complications such as headaches, nausea, stroke, and anosmia. However, the neurotropism of SARS-CoV-2 infection remains largely unknown. This study investigated the neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan, early strain) in K18-hACE2 mice. Despite both the variants inducing similar pathogenic patterns in various organs, B1.617.2-infected K18-hACE2 mice demonstrated a higher range of disease phenotypes such as weight loss, lethality, and conjunctivitis when compared to those in Hu-1-infected mice. In addition, histopathological analysis revealed that B1.617.2 infects the brain of K18-hACE2 mice more rapidly and effectively than Hu-1. Finally, we discovered that, in B1.617.2-infected mice, the early activation of various signature genes involved innate cytokines and that the necrosis-related response was most pronounced than that in Hu-1-infected mice. The present findings indicate the neuroinvasive properties of SARS-CoV-2 variants in K18-hACE2 mice and link them to fatal neuro-dissemination during the disease onset.