bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative John–Nirenberg inequalities at different scales
Authors: Martínez-Perales Javier C. , Rela Ezequiel , Rivera-Ríos Israel P.
Published: June 2022

Given a family $${\mathcal {Z}}=\{\Vert \cdot \Vert _{Z_Q}\}$$

Z
=
{
‖
·

‖

Z
Q

}

of norms or quasi-norms with uniformly bounded triangle inequality constants, where each Q is a cube in $${\mathbb {R}}^n$$

R

n

, we provide an abstract estimate of the form $$\begin{aligned} \Vert f-f_{Q,\mu }\Vert _{Z_Q}\le c(\mu )\psi ({\mathcal {Z}})\Vert f\Vert _{\mathrm {BMO}(\mathrm {d}\mu )} \end{aligned}$$

‖
f
-

f

Q
,
μ

‖

Z
Q

≤
c

(
μ
)

ψ

(
Z
)

‖
f
‖

BMO
(
d
μ
)

for every function $$f\in \mathrm {BMO}(\mathrm {d}\mu )$$

f
∈
BMO
(
d
μ
)

, where $$\mu $$
μ
is a doubling measure in $${\mathbb {R}}^n$$

R

n

and $$c(\mu )$$

c
(
μ
)

and $$\psi ({\mathcal {Z}})$$

ψ
(
Z
)

are positive constants depending on $$\mu $$
μ
and $${\mathcal {Z}}$$
Z
, respectively. That abstract scheme allows us to recover the sharp estimate $$\begin{aligned} \Vert f-f_{Q,\mu }\Vert _{L^p \left( Q,\frac{\mathrm {d}\mu (x)}{\mu (Q)}\right) }\le c(\mu )p\Vert f\Vert _{\mathrm {BMO}(\mathrm {d}\mu )}, \qquad p\ge 1 \end{aligned}$$

‖
f
-

f

Q
,
μ

‖

L
p

Q
,

d
μ
(
x
)

μ
(
Q
)

≤
c

(
μ
)

p

‖
f
‖

BMO
(
d
μ
)

,

p
≥
1

for every cube Q and every $$f\in \mathrm {BMO}(\mathrm {d}\mu )$$

f
∈
BMO
(
d
μ
)

, which is known to be equivalent to the John–Nirenberg inequality, and also enables us to obtain quantitative counterparts when $$L^p$$

L
p

is replaced by suitable strong and weak Orlicz spaces and $$L^{p(\cdot )}$$

L

p
(
·
)

spaces. Besides the aforementioned results we also generalize [(Ombrosi in Isr J Math 238:571-591, 2020), Theorem 1.2] to the setting of doubling measures and obtain a new characterization of Muckenhoupt’s $$A_\infty $$

A
∞

weights.
Identifying lexical change in negative word-of-mouth on social media
Authors: Strathern Wienke , Ghawi Raji , Schönfeld Mirco , Pfeffer Jürgen
Published: June 2022

Negative word-of-mouth is a strong consumer and user response to dissatisfaction. Moral outrages can create an excessive collective aggressiveness against one single argument, one single word, or one action of a person resulting in hateful speech. In this work, we examine the change of vocabulary to explore the outbreak of online firestorms on Twitter. The sudden change of an emotional state can be captured in language. It reveals how people connect with each other to form outrage. We find that when users turn their outrage against somebody, the occurrence of self-referencing pronouns like ‘I’ and ‘me’ reduces significantly. Using data from Twitter, we derive such linguistic features together with features based on retweets and mention networks to use them as indicators for negative word-of-mouth dynamics in social media networks. Based on these features, we build three classification models that can predict the outbreak of a firestorm with high accuracy.
Stochastic model describing evolution of microstructural parameters during hot rolling of steel plates and strips
Authors: Szeliga Danuta , Czyżewska Natalia , Klimczak Konrad , Kusiak Jan , Kuziak Roman , Morkisz Paweł , Oprocha Piotr , Pietrzyk Maciej , Poloczek Łukasz , Przybyłowicz Paweł
Published: June 2022

Enhancing strength-ductility synergy of materials has been for decades an objective of research on structural metallic materials. It has been shown by many researchers that significant improvement of this synergy can be obtained by tailoring heterogeneous multiphase microstructures. Since large gradients of properties in these microstructures cause a decrease of the local fracture resistance, the objective of research is to obtain smoother gradients of properties by control of the manufacturing process. Advanced material models are needed to design such microstructures with smooth gradients. These models should supply information about distributions of various microstructural features, instead of their average values. Models based on stochastic internal variables meet this requirement. Our objective was to account for the random character of the recrystallization and to transfer this randomness into equations describing the evolution of dislocations and grain size during hot deformation and during interpass times. The idea of this stochastic model is described in the paper. Experiments composed of uniaxial compression tests were performed to supply data for the identification and verification of the model in the hot deformation and static recrystallization parts. Histograms of the grain size were measured after hot deformation and at different times after the end of deformation. Identification and validation of the model were performed. The validated model, which predicts evolution of heterogeneous multiphase microstructure, is the main output of our work. The model was implemented in the finite element program for hot rolling of plates and sheets and simulations of these processes were performed. The model’s capability to compare and evaluate various rolling strategies are demonstrated in the paper.
Review of the state of the art in autonomous artificial intelligence
Authors: Radanliev Petar , De Roure David
Published: June 2022

This article presents a new design for autonomous artificial intelligence (AI), based on the state-of-the-art algorithms, and describes a new autonomous AI system called ‘AutoAI’. The methodology is used to assemble the design founded on self-improved algorithms that use new and emerging sources of data (NEFD). The objective of the article is to conceptualise the design of a novel AutoAI algorithm. The conceptual approach is used to advance into building new and improved algorithms. The article integrates and consolidates the findings from existing literature and advances the AutoAI design into (1) using new and emerging sources of data for teaching and training AI algorithms and (2) enabling AI algorithms to use automated tools for training new and improved algorithms. This approach is going beyond the state-of-the-art in AI algorithms and suggests a design that enables autonomous algorithms to self-optimise and self-adapt, and on a higher level, be capable to self-procreate.
Son preference and low birth weight for girls
Authors: Cho Hyunkuk
Published: June 2022

While previous studies have confirmed the negative effects of son preference on the prenatal care received by girls, few have examined its effect on birth outcomes. This study contributes to the literature on son preference by examining this relationship. The degree of son preference is measured by the sex ratio at birth, and the data were obtained from the birth registry of South Korea, which has a long history of strong son preference. We find that girls are more likely to be born with low birth weight when son preference is stronger. In addition, when son preference is stronger, girls are more likely to be born outside hospitals, which implies that mothers conceiving girls make fewer prenatal visits to the hospital when their son preference is stronger.
Pharmacist gender and physician acceptance of antibiotic stewardship recommendations: An analysis of the reducing overuse of antibiotics at discharge home intervention
Authors: Vaughn Valerie M. , Giesler Daniel L. , Mashrah Daraoun , Brancaccio Adamo , Sandison Katie , Spivak Emily S. , Szymczak Julia E. , Wu Chaorong , Horowitz Jennifer K. , Bashaw Linda , Hersh Adam L.
Published: June 2022

Objective:

To assess association of pharmacist gender with acceptance of antibiotic stewardship recommendations.

Design:

A retrospective evaluation of the Reducing Overuse of Antibiotics at Discharge (ROAD) Home intervention.

Setting:

The study was conducted from May to October 2019 in a single academic medical center.

Participants:

The study included patients receiving antibiotics on a hospitalist service who were nearing discharge.

Methods:

During the intervention, clinical pharmacists (none who had specialist postgraduate infectious disease residency training) reviewed patients on antibiotics and led an antibiotic timeout (ie, structured conversation) prior to discharge to improve discharge antibiotic prescribing. We assessed the association of pharmacist gender with acceptance of timeout recommendations by hospitalists using logistic regression controlling for patient characteristics.

Results:

Over 6 months, pharmacists conducted 295 timeouts: 158 timeouts (53.6%) were conducted by 12 women, 137 (46.4%) were conducted by 8 men. Pharmacists recommended an antibiotic change in 82 timeouts (27.8%), of which 51 (62.2%) were accepted. Compared to male pharmacists, female pharmacists were less likely to recommend a discharge antibiotic change: 30 (19.0%) of 158 versus 52 (38.0%) of 137 (P < .001). Female pharmacists were also less likely to have a recommendation accepted: 10 (33.3%) of 30 versus 41 (8.8%) of 52 (P < .001). Thus, timeouts conducted by female versus male pharmacists were less likely to result in an antibiotic change: 10 (6.3%) of 158 versus 41 (29.9%) of 137 (P < .001). After adjustments, pharmacist gender remained significantly associated with whether recommended changes were accepted (adjusted odds ratio [aOR], 0.10; 95%confidence interval [CI], 0.03–0.36 for female versus male pharmacists).

Conclusions:

Antibiotic stewardship recommendations made by female clinical pharmacists were less likely to be accepted by hospitalists. Gender bias may play a role in the acceptance of clinical pharmacist recommendations, which could affect patient care and outcomes.
The Belfast Boycott: consumerism and gender in revolutionary Ireland (1920–1922)
Authors: Omans Katie
Published: June 2022

The Belfast Boycott was a protest designed to dislodge loyalism in Northern Ireland, punish its adherents for perceived intolerance toward Catholics and end Irish partition. The boycott was set off by the expulsion of several thousand Catholic workers from employment in Belfast in July 1920. A total boycott of all goods coming from Belfast was implemented by the Dáil in September 1920. Boycotting provided Irish nationalists with an alternative to violent retaliation that allowed for the participation of a wider segment of the Irish population and diaspora in the revolutionary movement. However, such mass mobilisation meant that nationalists had to entrust their plan for an independent Ireland to a segment of the population that they overwhelmingly viewed as politically and economically uninformed: Irish women. The boycott offers a new vantage point from which to view the actions of and attitudes towards women and the role of mass mobilisation during the revolution. This article explores nationalists’ conceptions of Irish identity, the intersection between consumerism and patriotism, and the role that women played as both political and economic actors throughout the Irish revolutionary period.
‘Her own and her children's share’: luck, misogyny and imaginative resistance in twentieth-century Irish folklore
Authors: Brophy Christina S.
Published: June 2022

In twentieth-century Irish folklore, luck had much to do with women. While women were rarely seen as legitimate possessors of good fortune, luck was frequently perceived as being communicated through women's bodies and lost as a result of their actions. A caul, an intact amniotic membrane over a newborn's head and by-product of a pregnant woman's body, was believed to convey luck and health to either the mother or the child but not to both. The emphasis in this tradition on women's corporeality cast women and their maternal by-products as appropriable familial and communal resources. This and additional lore reveal that women were constructed as dangerous, ‘object-like others’ whose mere presence could threaten men's safety. Twentieth-century Ireland's folk and political cultures each operated within frameworks of supporting ideological systems. Despite being easily distinguishable in articulation, these cultures were frequently in concert with one another, especially relating to prescriptive gender roles. In numerous instances, lore about luck bolstered legislative, social and religious policies of the Irish Free State and the early Irish Republic regarding women. However, narrow divergences allowed women limited space to contest gender hierarchy in folk communities. Some women found opportunities for subversion in the very cultural fabric that restricted them, resorting to imaginative resistance to reject and counter misogynist discourse and assert female subjectivity.
Prevalence of vitamin A deficiency in women of childbearing age in Brazil: a systematic review and meta-analysis
Authors: Ferreira Carolina Müller , Silva Marcus Tolentino , de Oliveira Julicristie Machado , Höfelmafnn Doroteia Aparecida , Alves Daniela Fernanda dos Santos , da Silva Wesley Willian Gomes , Galvão Tais Freire
Published: June 2022

Vitamin A is an essential micronutrient, especially during pregnancy. We aimed to assess the prevalence of vitamin A deficiency in Brazilian women of childbearing age. We conducted a systematic review with meta-analysis of studies that assessed vitamin A deficiency in women of childbearing age following the registered protocol (CRD42020171856). Independent peer researchers selected the studies retrieved from MEDLINE, Embase, Scopus and other sources. Data from the eligible studies were extracted in pairs and assessed for methodological quality. The prevalence of vitamin A deficiency (< 0·70 µmol/l or <0·20 µg/dl) and 95 % CI was combined by meta-analysis, and heterogeneity was estimated byI2. Out of 3610 screened records, thirty-two studies were included, which assessed 12 577 women from 1965 to 2017, mostly in maternity hospitals. Main limitations of the studies were in sample frame (30/32) and sampling method (29/32). Deficiency occurred in 13 % (95 % CI 9·4, 17·2 %;I²= 97 %) of all women and was higher in pregnant women (16·1 %; 95 % CI 5·6, 30·6 %;I²= 98 %) than non-pregnant women (12·3 %; 95 % CI 8·4, 16·8 %;I²= 96 %). The prevalence increased according to the decade, from 9·5 % (95 % CI 1·9–21·6 %;I²= 98 %) up to 1990, 10·8 % (95 % CI 7·9, 14·2 %;I²= 86 %) in the 2000s and 17·8 % (95 % CI 8·7, 29·0 %;I²= 98 %) in the 2010s. Over 10 % of Brazilian women in childbearing age were deficient in vitamin A. Higher prevalence was observed in pregnant women, and deficiency seemed to be increasing over the decades. Low representativeness of the studies, mainly based on convenience sampling that included pregnant, postpartum, lactating and non-pregnant women, as well as high heterogeneity, limits the findings.
Identification and expression patterns of candidate carboxylesterases in Carposina sasakii Matsumura (Lepidoptera: Carposinidae), an important pest of fruit trees
Authors: Li Jia , Zhang Long
Published: June 2022

Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is an important pest of fruit trees in a large area of Asia. The adults mainly depend on olfaction to communicate with the environment, but the olfactory mechanism has not been well known. Odorant degrading enzymes (ODEs) are important olfactory proteins, which inactivate and degrade odorants to free odorant receptors for maintaining olfactory sensitivity. Carboxylesterases (CXEs) are considered to be a major group of moth ODEs. In this study, four candidate CXEs (CsasCXE1 ~ CsasCXE4) were identified by using head transcriptomic data from C. sasakii adult females and males. Sequence alignment showed conserved amino acid residues and their variations in C. sasakii CXEs. Phylogenetic analysis indicated the CXEs with the variations cluster well, and each C. sasakii CXE clusters in a clade with some of the other lepidopteran CXEs, with a high enough bootstrap value. Gene expression analysis revealed that CsasCXE2 and CsasCXE3 have similar tissue and sex expression patterns in C. sasakii adults. The two CXEs have relatively high expression levels in the heads and are expressed more abundantly in the female heads than male heads. CsasCXE1 and CsasCXE4 are expressed at higher levels in the male heads than female heads, but not dominantly expressed in the heads among the different tissues. Whether these CXEs function as ODEs remains to be further researched. This study laid the foundation for exploring functions of C. sasakii CXEs.
Precarity's Pirate: The Fictive Afterlives of Idemitsu Sazō
Authors: Leheny David
Published: June 2022

When the famously nationalistic Japanese author Hyakuta Naoki published his best-selling novelA Man Called Pirate(Kaizoku to yobareta otoko) in 2012, which subsequently became both a manga and a major film, he renewed interest in the midcentury oil baron Idemitsu Sazō, using him as the model for the novel's lead character. Hyakuta claims to have aimed to inspire the country, reeling from decades of slow growth as well as the 2011 tsunami and nuclear disaster, by featuring a visionary Japanese leader motivated primarily by love for his employees and his country. This article traces the efforts across these media to render Idemitsu as a credible character, particularly in dealing with his real-life family as well as his “family” of employees. It argues that the partial disappearance of the “real” Idemitsu in these versions of Hyakuta's novel allowed the production of a more believable one—made believable in part because of the essential Japanese values that he ostensibly represents, even as the constraints on these representations hint at fissures and tensions in contemporary political use of biographical fiction and film.
“Mechanization Takes Command?”: Powered Machinery and Production Times in Late Nineteenth-Century American Manufacturing
Authors: Atack Jeremy , Margo Robert A. , Rhode Paul W.
Published: June 2022

During the nineteenth century, U.S. manufacturers shifted away from the “hand labor” mode of production, characteristic of artisan shops, to “machine labor,” which was increasingly concentrated in steam-powered factories. This transition fundamentally changed production tasks, jobs, and job requirements. This paper uses digitized data on these two production modes from an 1899 U.S. Commissioner of Labor report to estimate the frequency and impact of the use of inanimate power on production operation times. About half of production operations were mechanized; the use of inanimate power raised productivity, accounting for about one-quarter to one-third of the overall productivity advantage of machine labor. However, additional factors, such as the increased division of labor and adoption of high-volume production, also played quantitatively important roles in raising productivity in machine production versus by hand.
A Permutation Entropy Analysis of Voyager Interplanetary Magnetic Field Observations
Authors: Raath J. L. , Olivier C. P. , Engelbrecht N. E.
Published: June 2022

The permutation entropy analysis technique is here employed to study Voyager 2 observations of heliospheric field fluctuations from ∼6 AU to ∼34 AU for the first time. The properties of the technique, especially regarding the classification of a given process as either chaotic or stochastic, are illustrated in some detail and it is indicated how the technique is best applied and interpreted to the data set in question. Proceeding from this, conclusions are made regarding the stochasticity of the processes driving turbulence as a function of radial distance from the Sun, which is here found to increase with distance toward a value theoretically associated with Brownian motion, exceeding that value depending on the data bin size considered. At larger radial distances, however, it is argued that this trend may be influenced by a strongly declining signal‐to‐noise ratio. Intriguingly, this technique also serves to identify intervals of anomalously moderate to low stochasticity, which are briefly investigated here.
A Small CO2 Leakage May Induce Seismicity on a Sub‐Seismic Fault in a Good‐Porosity Clastic Saline Aquifer
Authors: Glubokovskikh Stanislav , Saygin Erdinc , Shapiro Serge , Gurevich Boris , Isaenkov Roman , Lumley David , Nakata Rie , Drew Julian , Pevzner Roman
Published: June 2022

Despite public concerns, only a few CO2 injections into saline aquifers have reported microseismicity. We analyze passive seismic monitoring of a small (15,000 tonnes and 0.15 MPa pressure) injection of supercritical CO2‐rich mixture for Stage 2C of the CO2CRC Otway Project (Victoria, Australia), which induced 19 detectable events with maximum moment magnitude MW‐0.5. The locations and dynamic parameters of the triggered events indicate a reactivation of a small fault patch where CO2 flowed through the fault. Time‐lapse seismic images of the plume and reservoir simulations show that the reactivation occurred when the CO2 plume reached this fault. This might be indicative of a fault weakening by the plume that enabled subsequent reactivation by pressure variations. Our observations suggest that a leakage from a commercial‐scale storage may trigger felt seismicity in the overburden without strong overpressure, thus, the de‐risking workflows should involve a detailed study of small faults.
New Occurrence of Seifertite and Stishovite in Chang’E‐5 Regolith
Authors: Pang Runlian , Yang Jing , Du Wei , Zhang Aicheng , Liu Shirong , Li Rui
Published: June 2022

High‐pressure minerals in impact ejecta quantify shock conditions and provide clues for provenance analysis. The sampling site of Chang’E‐5 may contain distal ejecta, which is critical for constraining the impact events and interpreting the constitution of the target geological units. Here, we report a silica fragment consisting of seifertite, stishovite, α‐cristobalite‐like phase, and silica glass in Chang’E‐5 regolith. Both seifertite and stishovite formed via solid‐state transformation mechanism, in which seifertite formed by transition from α‐cristobalite upon pressure loading whereas stishovite may form from seifertite when postshock temperature was significant during pressure release. The coexistence of seifertite and stishovite suggests that their host rock has experienced a peak shock pressure of 11–40 GPa and records different stages of the impact process. Crater size calculation revealed that the host rock of stishovite and seifertite could have been transported from distant craters, confirming the retention of distal ejecta in Chang’E‐5 landing site.
Arrival of New Great Salinity Anomaly Weakens Convection in the Irminger Sea
Authors: Biló T. C. , Straneo F. , Holte J. , Le Bras I. A.‐A.
Published: June 2022

The Subpolar North Atlantic is prone to recurrent extreme freshening events called Great Salinity Anomalies (GSAs). Here, we combine hydrographic ocean analyses and moored observations to document the arrival, spreading, and impacts of the most recent GSA in the Irminger Sea. This GSA is associated with a rapid freshening of the upper Irminger Sea between 2015 and 2020, culminating in annually averaged salinities as low as the freshest years of the 1990s and possibly since 1960. Upon the GSA propagation into the Irminger Sea over the Reykjanes Ridge, the boundary currents rapidly advected its signal around the basin within months while fresher waters slowly spread and accumulated into the interior. The anomalies in the interior freshened waters produced by deep convection during the 2017–2018 winter and actively contributed to the suppression of deep convection in the following two winters.
MagNet: Automated Magnetic Mineral Grain Morphometry Using Convolutional Neural Network
Authors: Pei Zhaowen , Chang Liao , Xue Pengfei , Harrison Richard J.
Published: June 2022

Morphometry (i.e., the quantitative determination of grain size and shape information) is an essential component of all rock and environmental magnetic studies. Electron microscopy is often used to image magnetic mineral grains, but the current lack of systematic image processing tools makes it challenging to quantify key morphological features of magnetic minerals in natural samples. Here, we present an easy‐to‐use machine learning framework MagNet for automated morphological recognition of magnetic mineral grains in microscopic images. This framework, based on a convolutional neural network, performs well in the recognition and classification of magnetofossil nanoparticles in transmission electron microscopy images after training and testing. MagNet is open‐source and can easily be extended to process different types of mineral images. This tool has the potential, therefore, to extract key quantitative information of magnetic mineral populations within heterogeneous terrestrial and meteoritic samples for the interpretations of Earth and planetary processes.
Glucocorticoid-induced expansion of classical monocytes contributes to bone loss
Authors: Liu Pei , Gao Youshui , Luo Pengbo , Yu Hongping , Guo Shang , Liu Fuyun , Gao Junjie , Xu Jianzhong , Wang Shengdian , Zhang Changqing
Published: June 2022

Classical monocytes are commonly involved in the innate inflammatory response and are the progenitors of osteoclasts. Excess endogenous glucocorticoids (GCs) can increase the levels of classical monocytes in blood and bone marrow. The role of this cell population in high-dose exogenous GC-induced osteoporosis (GIOP) remains to be elucidated. In this study, GIOP was established in rats and mice by daily methylprednisolone injection, and monocyte subsets were analyzed by flow cytometry. We demonstrated that classical monocytes accumulate in bone marrow during GIOP. Similarly, the monocyte proportion among bone marrow nucleated cells was also increased in patients with steroid treatment history. We sorted classical monocytes and analyzed their transcriptional profile in response to GCs by RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that classical monocytes isolated from GC-treated rats exhibited osteoclast differentiation potential. Deletion of classical monocytes by clodronate liposome treatment prevented GIOP via inhibition of osteoclastogenesis and restoration of CD31HiendomucinHi vessels. Regarding the molecular mechanism, classical monocytes express high levels of glucocorticoid receptors. In vitro treatment with GCs increased both the percentage and absolute number of monocytes and promoted their proliferation. In summary, classical monocytes mediated GC-induced bone loss and are a potential target for therapeutic intervention in GIOP treatment.
Temporal modulation brings metamaterials into new era
Authors: Yuan Luqi , Fan Shanhui
Published: June 2022

Temporal modulations in photonics bring many exotic optical phenomena in the time dimension while metamaterials provide powerful ways in manipulating light in the spatial domain. The authors envision the connection, Floquet Metamaterials, may deliver novel opportunities in nanophotonics.
Prenatal hypoxia alters the early ontogeny of dopamine neurons
Authors: Brandon Anastasia , Cui Xiaoying , Luan Wei , Ali Asad Amanat , Pertile Renata Aparecida Nedel , Alexander Suzanne Adele , Eyles Darryl Walter
Published: June 2022

Dopaminergic (DA) dysfunction is a significant feature in the pathophysiology of schizophrenia. Established developmental risk factors for schizophrenia such as maternal immune activation (MIA) or developmental vitamin D (DVD) deficiency, when modelled in animals, reveal the differentiation of early DA neurons in foetal brains is delayed suggesting this may be a convergent aetiological pathway. Here we have assessed the effects of prenatal hypoxia, another well-known developmental risk factor for schizophrenia, on developing DA systems. Pregnant mice were exposed to a hypoxic environment of 10% oxygen for 48 h from embryonic day 10 (E10) to E12. Embryonic brains were collected and the positioning of mesencephalic cells, expression of DA specification and maturation factors were examined along with the expression of factors that may govern the migration of these neurons. We show that prenatal hypoxia results in a decrease in dopaminergic progenitors retards early DA neuron lateral migration and reduces expression of the receptors known to govern this process. A second time-point, postnatal day 10 (P10) was also examined in order to assess whether prenatal hypoxia alters early presynaptic architecture in the developing striatum. We show reduced expression of tyrosine hydroxylase (TH) in the postnatal striatum along with increases in the density of high-probability DA release sites within TH varicosities. These findings add to the emerging literature showing that multiple epidemiologically validated environmental risk factors for schizophrenia may induce early alterations to develop DA systems. This may represent a possible convergent mechanism in the onset of presynaptic DA dysfunction in patients.
Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway
Authors: Wang Shi-Jun , Qiu Zhen-Zhen , Chen Fu-Wei , Mao An-Li , Bai Jun-Chao , Hong Ye-Jing , Zhang Zhong-Pan , Zhu Wu-An , Zhang Zhi-Wei , Zhou Hao
Published: June 2022

Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) in renal fibrosis. EVs released by bone marrow mesenchymal stem cells (BMSCs) contain miR-181d, which may represent a potential therapy for renal fibrosis. miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), which activates the nuclear factor-kappa B (NF-κB) signaling pathway. Luciferase assays were performed to confirm the relationship between miR-181d and KLF6. Gain- and loss-of-function studies in vivo and in vitro were performed to assess the effect of BMSC-derived EVs (BMSC-EVs), which contained miR-181d, on KLF6, NF-κB, and renal fibrosis. Transforming growth factor-β (TGF-β)-induced renal tubular epithelial HK-2 cells were treated with EVs derived from BMSCs followed by evaluation of collagen type IV α1 (Col4α1), Collagen I and α-smooth muscle actin (α-SMA) as indicators of the extent of renal fibrosis. Renal fibrosis was induced in rats by unilateral ureteral obstruction (UUO) followed by the subsequent analysis of fibrotic markers. BMSC-EVs had higher miR-181d expression. Overexpression of miR-181d correlated with a decrease in KLF6 expression as well as the levels of IκBα phosphorylation, α-SMA, Col4α1, TGF-βR1 and collagen I in HK-2 cells. In vivo, treatment with miR-181d-containing BMSC-derived EVs was able to restrict the progression of fibrosis in UUO-induced rats. Together, BMSC-EVs suppress fibrosis in vitro and in vivo by delivering miR-181d to neighboring cells, where it targets KLF6 and inhibits the NF-κB signaling pathway.
Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis
Authors: Yang Yang , Sheng Jindong , Hu Shuai , Cui Yun , Xiao Jing , Yu Wei , Peng Jing , Han Wenke , He Qun , Fan Yu , Niu Yuanjie , Lin Jun , Tian Ye , Chang Chawnshang , Yeh Shuyuan , Jin Jie
Published: June 2022

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.
CCAR2 controls mitotic progression through spatiotemporal regulation of Aurora B
Authors: Ryu Jaewook , Kim Ja-Eun
Published: June 2022

CCAR2 (cell cycle and apoptosis regulator 2) is a multifaceted protein involved in cell survival and death following cytotoxic stress. However, little is known about the physiological functions of CCAR2 in regulating cell proliferation in the absence of external stimuli. The present study shows that CCAR2-deficient cells possess multilobulated nuclei, suggesting a defect in cell division. In particular, the duration of mitotic phase was perturbed. This disturbance of mitotic progression resulted from premature loss of cohesion with the centromere, and inactivation of the spindle assembly checkpoint during prometaphase and metaphase. It resulted in the formation of lagging chromosomes during anaphase, leading ultimately to the activation of the abscission checkpoint to halt cytokinesis. The CCAR2-dependent mitotic progression was related to spatiotemporal regulation of active Aurora B. In conclusion, the results suggest that CCAR2 governs mitotic events, including proper chromosome segregation and cytokinetic division, to maintain chromosomal stability.
A novel mRNA decay inhibitor abolishes pathophysiological cellular transition
Authors: Kami Daisuke , Ishizaki Toshimasa , Taya Toshihiko , Katoh Akira , Kouji Hiroyuki , Gojo Satoshi
Published: June 2022

In cells, mRNA synthesis and decay are influenced by each other, and their balance is altered by either external or internal cues, resulting in changes in cell dynamics. We previously reported that it is important that an array of mRNAs that shape a phenotype are degraded before cellular transitions, such as cellular reprogramming and differentiation. In adipogenesis, the interaction between DDX6 and 4E-T had a definitive impact on the pathway in the processing body (PB). We screened a library of α-helix analogs with an alkaloid-like backbone to identify compounds that inhibit the binding between DDX6 and 4E-T proteins, which occurs between the α-helix of structured and internally disordered proteins. IAMC-00192 was identified as a lead compound. This compound directly inhibited the interaction between DDX6 and 4E-T. IAMC-00192 inhibited the temporal increase in PB formation that occurs during adipogenesis and epithelial-mesenchymal transition (EMT) and significantly suppressed these cellular transitions. In the EMT model, the half-life of preexisting mRNAs in PBs was extended twofold by the compound. The novel inhibitor of RNA decay not only represents a potentially useful tool to analyze in detail the pathological conditions affected by RNA decay and how it regulates the pathological state. The identification of this inhibitor may lead to the discovery of a first-in-class RNA decay inhibitor drug.
Structural insights into human brain–gut peptide cholecystokinin receptors
Authors: Ding Yu , Zhang Huibing , Liao Yu-Ying , Chen Li-Nan , Ji Su-Yu , Qin Jiao , Mao Chunyou , Shen Dan-Dan , Lin Lin , Wang Hao , Zhang Yan , Li Xiao-Ming
Published: June 2022

The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain–gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to Gs and Gq, whereas CCK2R primarily couples to Gq. Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R–Gs signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R–Gq complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain–gut axis.
Dual chirped microcomb based parallel ranging at megapixel-line rates
Authors: Lukashchuk Anton , Riemensberger Johann , Karpov Maxim , Liu Junqiu , Kippenberg Tobias J.
Published: June 2022

Laser-based ranging (LiDAR) - already ubiquitously used in industrial monitoring, atmospheric dynamics, or geodesy - is a key sensor technology. Coherent laser ranging, in contrast to time-of-flight approaches, is immune to ambient light, operates continuous-wave allowing higher average powers, and yields simultaneous velocity and distance information. State-of-the-art coherent single laser-detector architectures reach hundreds of kilopixel per second sampling rates, while emerging applications - autonomous driving, robotics, and augmented reality - mandate megapixel per second point sampling to support real-time video-rate imaging. Yet, such rates of coherent LiDAR have not been demonstrated. Recent advances in photonic chip-based microcombs provide a route to higher acquisition speeds via parallelization but require separation of individual channels at the detector side, increasing photonic integration complexity. Here we overcome the challenge and report a hardware-efficient swept dual-soliton microcomb technique that achieves coherent ranging and velocimetry at megapixel per second line scan measurement rates with up to 64 optical channels. Multiheterodyning two synchronously frequency-modulated microcombs yields distance and velocity information of all individual ranging channels on a single receiver alleviating the need for individual separation, detection, and digitization. The reported LiDAR implementation is compatible with photonic integration and demonstrates the significant advantages of acquisition speed afforded by the convergence of optical telecommunication and metrology technologies.
Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis
Authors: Ko Toshiyuki , Nomura Seitaro , Yamada Shintaro , Fujita Kanna , Fujita Takanori , Satoh Masahiro , Oka Chio , Katoh Manami , Ito Masamichi , Katagiri Mikako , Sassa Tatsuro , Zhang Bo , Hatsuse Satoshi , Yamada Takanobu , Harada Mutsuo , Toko Haruhiro , Amiya Eisuke , Hatano Masaru , Kinoshita Osamu , Nawata Kan , Abe Hiroyuki , Ushiku Tetsuo , Ono Minoru , Ikeuchi Masashi , Morita Hiroyuki , Aburatani Hiroyuki , Komuro Issei
Published: June 2022

Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, and genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) is a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure overload downregulates expression of Htra3 in cardiac fibroblasts and activated TGF-β signaling, which induces not only cardiac fibrosis but also heart failure through DNA damage accumulation and secretory phenotype induction in failing cardiomyocytes. Overexpression of Htra3 in the heart inhibits TGF-β signaling and ameliorates cardiac dysfunction after pressure overload. Htra3-regulated induction of spatio-temporal cardiac fibrosis and cardiomyocyte secretory phenotype are observed specifically in infarct regions after myocardial infarction. Integrative analyses of single-cardiomyocyte transcriptome and plasma proteome in human reveal that IGFBP7, which is a cytokine downstream of TGF-β and secreted from failing cardiomyocytes, is the most predictable marker of advanced heart failure. These findings highlight the roles of cardiac fibroblasts in regulating cardiomyocyte homeostasis and cardiac fibrosis through the Htra3-TGF-β-IGFBP7 pathway, which would be a therapeutic target for heart failure.
Switching the NIR upconversion of nanoparticles for the orthogonal activation of photoacoustic imaging and phototherapy
Authors: Yang Yang , Huang Jinshu , Wei Wei , Zeng Qin , Li Xipeng , Xing Da , Zhou Bo , Zhang Tao
Published: June 2022

Phototheranostics based on upconversion nanoparticles (UCNPs) offer the integration of imaging diagnostics and phototherapeutics. However, the programmable control of the photoactivation of imaging and therapy with minimum side effects is challenging due to the lack of ideal switchable UCNPs agents. Here we demonstrate a facile strategy to switch the near infrared emission at 800 nm from rationally designed UCNPs by modulating the irradiation laser into pulse output. We further synthesize a theranostic nanoagent by combining with a photosensitizer and a photoabsorbing agent assembled on the UCNPs. The orthogonal activation of in vivo photoacoustic imaging and photodynamic therapy can be achieved by altering the excitation modes from pulse to continuous-wave output upon a single 980 nm laser. No obvious harmful effects during photoexcitation was identified, suggesting their use for long-term imaging-guidance and phototherapy. This work provides an approach to the orthogonal activation of imaging diagnostics and photodynamic therapeutics.
Optical linewidth of soliton microcombs
Authors: Lei Fuchuan , Ye Zhichao , Helgason Óskar B. , Fülöp Attila , Girardi Marcello , Torres-Company Victor
Published: June 2022

Soliton microcombs provide a versatile platform for realizing fundamental studies and technological applications. To be utilized as frequency rulers for precision metrology, soliton microcombs must display broadband phase coherence, a parameter characterized by the optical phase or frequency noise of the comb lines and their corresponding optical linewidths. Here, we analyse the optical phase-noise dynamics in soliton microcombs generated in silicon nitride high-Q microresonators and show that, because of the Raman self-frequency shift or dispersive-wave recoil, the Lorentzian linewidth of some of the comb lines can, surprisingly, be narrower than that of the pump laser. This work elucidates information about the physical limits in phase coherence of soliton microcombs and illustrates a new strategy for the generation of spectrally coherent light on chip.
Berry curvature-induced local spin polarisation in gated graphene/WTe2 heterostructures
Authors: Powalla Lukas , Kiemle Jonas , König Elio J. , Schnyder Andreas P. , Knolle Johannes , Kern Klaus , Holleitner Alexander , Kastl Christoph , Burghard Marko
Published: June 2022

Experimental control of local spin-charge interconversion is of primary interest for spintronics. Van der Waals (vdW) heterostructures combining graphene with a strongly spin-orbit coupled two-dimensional (2D) material enable such functionality by design. Electric spin valve experiments have thus far provided global information on such devices, while leaving the local interplay between symmetry breaking, charge flow across the heterointerface and aspects of topology unexplored. Here, we probe the gate-tunable local spin polarisation in current-driven graphene/WTe2 heterostructures through magneto-optical Kerr microscopy. Even for a nominal in-plane transport, substantial out-of-plane spin accumulation is induced by a corresponding out-of-plane current flow. We present a theoretical model which fully explains the gate- and bias-dependent onset and spatial distribution of the intense Kerr signal as a result of a non-linear anomalous Hall effect in the heterostructure, which is enabled by its reduced point group symmetry. Our findings unravel the potential of 2D heterostructure engineering for harnessing topological phenomena for spintronics, and constitute an important step toward nanoscale, electrical spin control.
Re-programming mouse liver-resident invariant natural killer T cells for suppressing hepatic and diabetogenic autoimmunity
Authors: Umeshappa Channakeshava Sokke , Solé Patricia , Yamanouchi Jun , Mohapatra Saswat , Surewaard Bas G. J. , Garnica Josep , Singha Santiswarup , Mondal Debajyoti , Cortés-Vicente Elena , D’Mello Charlotte , Mason Andrew , Kubes Paul , Serra Pau , Yang Yang , Santamaria Pere
Published: June 2022

Invariant NKT (iNKT) cells comprise a heterogeneous group of non-circulating, tissue-resident T lymphocytes that recognize glycolipids, including alpha-galactosylceramide (αGalCer), in the context of CD1d, but whether peripheral iNKT cell subsets are terminally differentiated remains unclear. Here we show that mouse and human liver-resident αGalCer/CD1d-binding iNKTs largely correspond to a novel Zbtb16+Tbx21+Gata3+MaflowRorc– subset that exhibits profound transcriptional, phenotypic and functional plasticity. Repetitive in vivo encounters of these liver iNKT (LiNKT) cells with intravenously delivered αGalCer/CD1d-coated nanoparticles (NP) trigger their differentiation into immunoregulatory, IL-10+IL-21-producing Zbtb16highMafhighTbx21+Gata3+Rorc– cells, termed LiNKTR1, expressing a T regulatory type 1 (TR1)-like transcriptional signature. This response is LiNKT-specific, since neither lung nor splenic tissue-resident iNKT cells from αGalCer/CD1d-NP-treated mice produce IL-10 or IL-21. Additionally, these LiNKTR1 cells suppress autoantigen presentation, and recognize CD1d expressed on conventional B cells to induce IL-10+IL-35-producing regulatory B (Breg) cells, leading to the suppression of liver and pancreas autoimmunity. Our results thus suggest that LiNKT cells are plastic for further functional diversification, with such plasticity potentially targetable for suppressing tissue-specific inflammatory phenomena.
Mafa-dependent GABAergic activity promotes mouse neonatal apneas
Authors: Lecoin Laure , Dempsey Bowen , Garancher Alexandra , Bourane Steeve , Ruffault Pierre-Louis , Morin-Surun Marie-Pierre , Rocques Nathalie , Goulding Martyn , Eychène Alain , Pouponnot Celio , Fortin Gilles , Champagnat Jean
Published: June 2022

While apneas are associated with multiple pathological and fatal conditions, the underlying molecular mechanisms remain elusive. We report that a mutated form of the transcription factor Mafa (Mafa4A) that prevents phosphorylation of the Mafa protein leads to an abnormally high incidence of breath holding apneas and death in newbornMafa4A/4Amutant mice. This apneic breathing is phenocopied by restricting the mutation to central GABAergic inhibitory neurons and by activation of inhibitory Mafa neurons while reversed by inhibiting GABAergic transmission centrally. We find that Mafa activates theGad2promoter in vitro and that this activation is enhanced by the mutation that likely results in increased inhibitory drives onto target neurons. We also find that Mafa inhibitory neurons are absent from respiratory, sensory (primary and secondary) and pontine structures but are present in the vicinity of the hypoglossal motor nucleus including premotor neurons that innervate the geniohyoid muscle, to control upper airway patency. Altogether, our data reveal a role for Mafa phosphorylation in regulation of GABAergic drives and suggest a mechanism whereby reduced premotor drives to upper airway muscles may cause apneic breathing at birth.