The inversion of inhomogeneous physical states has great technological importance; for example, active noise reduction relies on the emission of an inverted sound wave that interferes destructively ...with the noise of the emitter
, and inverting the evolution of a spin system by using a magnetic-field pulse enables magnetic resonance tomography
. In contrast to these examples, inversion of a distribution of ferromagnetic or ferroelectric domains within a material is surprisingly difficult: field poling creates a single-domain state, and piece-by-piece inversion using a scanning tip is impractical. Here we report inversion of entire ferromagnetic and ferroelectric domain patterns in the magnetoelectric material Co
TeO
and the multiferroic material Mn
GeO
, respectively. In these materials, an applied magnetic field reverses the magnetization or polarization, respectively, of each domain, but leaves the domain pattern intact. Landau theory indicates that this type of magnetoelectric inversion is universal across materials that exhibit complex ordering, with one order parameter holding the memory of the domain structure and another setting its overall sign. Domain-pattern inversion is only one example of a previously unnoticed effect in systems such as multiferroics, in which several order parameters are available for combination. Exploring these effects could therefore advance multiferroics towards new levels of functionality.
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KISLJ, NUK, SBMB, UL, UM, UPUK
Papillary thyroid carcinoma (PTC) is a well-differentiated thyroid tumor that accounts for approximately 80% of thyroid cancer cases. On other hand, anaplastic thyroid carcinoma (ATC) is a less ...frequent, but aggressive subtype, with poor prognosis. MicroRNAs (miRNAs), small non-coding RNAs, have emerged as potent post-transcriptional regulators of gene expression, which modulate the expression of cancer-related genes. Computational analyses estimate that a single miRNA may modulate hundreds of mRNA targets and, at the same time, cooperate with others to regulate one single mRNA transcript. Due to the large number of predicted targets and possible interactions, only a small number of miRNAs have characterized biological roles, and the panorama of miRNA-mediated regulation in thyroid cancer remains to be understood. Taking into consideration the large amount of gene expression data deposited in public databases we aligned miRNA target prediction and gene expression data from public PTC and ATC datasets to construct a network of post-transcriptional regulation in thyroid cancer. After a gene set enrichment analysis we identified signaling pathways and biological processes potentially modulated by the miRNAs deregulated in PTC and ATC. Our results show miRNA-mRNA interaction that could contribute with the de-regulation of key tumor-host mediators, such as extra-cellular matrix molecules, interleukins and interleukin receptors, which could drive a more aggressive behavior and tumor progression. Moreover, our analysis through The Cancer Genome Atlas (TCGA) database revealed that aberrant expression of ECM and cytokines genes is frequent in PTC and is associated with aggressive behavior and decreased overall survival rate. In conclusion, we shed light on the post-transcriptional regulation of gene expression in differentiated and undifferentiated thyroid cancers, revealing a potential role of miRNAs in modulation of tumor-host interaction molecules, particularly ECM molecules and immune system mediators, which could stimulate crosstalk between tumors and the immune system to generate a more aggressive behavior. We propose a novel putative miRNA:mRNA network that could lead to a new path toward functional studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context.
In the age of JWST, temperate terrestrial exoplanets transiting nearby late-type M dwarfs provide unique opportunities for characterising their atmospheres, as well as searching for ...biosignature gases. In this context, the benchmark TRAPPIST-1 planetary system has garnered the interest of a broad scientific community.
Aims.
We report here the discovery and validation of two temperate super-Earths transiting LP 890-9 (TOI-4306, SPECULOOS-2), a relatively low-activity nearby (32 pc) M6V star. The inner planet, LP 890-9 b, was first detected by TESS (and identified as TOI-4306.01) based on four sectors of data. Intensive photometric monitoring of the system with the SPECULOOS Southern Observatory then led to the discovery of a second outer transiting planet, LP 890-9 c (also identified as SPECULOOS-2 c), previously undetected by TESS. The orbital period of this second planet was later confirmed by MuSCAT3 follow-up observations.
Methods.
We first inferred the properties of the host star by analyzing its Lick/Kast optical and IRTF/SpeX near-infrared spectra, as well as its broadband spectral energy distribution, and
Gaia
parallax. We then derived the properties of the two planets by modelling multi-colour transit photometry from TESS, SPECULOOS-South, MuSCAT3, ExTrA, TRAPPIST-South, and SAINT-EX. Archival imaging, Gemini-South/Zorro high-resolution imaging, and Subaru/IRD radial velocities also support our planetary interpretation.
Results.
With a mass of 0.118 ± 0.002
M
⊙
, a radius of 0.1556 ± 0.0086
R
⊙
, and an effective temperature of 2850 ± 75 K, LP 890-9 is the second-coolest star found to host planets, after TRAPPIST-1. The inner planet has an orbital period of 2.73 d, a radius of 1.320
−0.027
+0.053
R
⊕
, and receives an incident stellar flux of 4.09 ± 0.12
S
⊕
. The outer planet has a similar size of 1.367
−0.039
+0.055
R
⊕
and an orbital period of 8.46 d. With an incident stellar flux of 0.906 ± 0.026
S
⊕
, it is located within the conservative habitable zone, very close to its inner limit (runaway greenhouse). Although the masses of the two planets remain to be measured, we estimated their potential for atmospheric characterisation via transmission spectroscopy using a mass-radius relationship and found that, after the TRAPPIST-1 planets, LP 890-9 c is the second-most favourable habitable-zone terrestrial planet known so far (assuming for this comparison a similar atmosphere for all planets).
Conclusions.
The discovery of this remarkable system offers another rare opportunity to study temperate terrestrial planets around our smallest and coolest neighbours.
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FMFMET, NUK, UL, UM, UPUK
Background
Liver fibrosis is a risk factor for hepatectomy but cannot be determined accurately before hepatectomy because diagnostic procedures are too invasive. Magnetic resonance elastography (MRE) ...can determine liver stiffness (LS), a surrogate marker for assessing liver fibrosis, non‐invasively. The aim of this study was to investigate whether the LS value determined by MRE is predictive of major complications after hepatectomy.
Methods
This prospective study enrolled consecutive patients who underwent hepatic resection between April 2013 and August 2016. LS values were measured by imaging shear waves by MRE in the liver before hepatectomy. The primary endpoint was major complications, defined as Clavien–Dindo grade IIIa or above. Logistic regression analysis identified independent predictive factors, from which a logistic model to estimate the probability of major complications was constructed.
Results
A total of 96 patients were included in the study. Major complications were observed in 15 patients (16 per cent). Multivariable logistic analysis confirmed that higher LS value (P = 0·021) and serum albumin level (P = 0·009) were independent predictive factors for major complications after hepatectomy. Receiver operating characteristic (ROC) analysis showed that the best LS cut‐off value was 4·3 kPa for detecting major complications, comparable to liver fibrosis grade F4, with a sensitivity of 80 per cent and specificity of 82 per cent. A logistic model using the LS value and serum albumin level to estimate the probability of major complications was constructed; the area under the ROC curve for predicting major complications was 0·84.
Conclusion
The LS value determined by MRE in patients undergoing hepatectomy was an independent predictive factor for major complications.
Liver stiffness predicts complications
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The objective numerical standard during an ECG test is only blood pressure and depends on the presence or absence of subjective symptoms. However, atrial fibrillation, which one of the arrhythmias ...detected by ECG, does not always occur during an examination without symptoms. We have developed a machine learning model to objectively provide recommendations regarding the conduct of ECGs in specific health checkups. Data used are ledger data, receipt data, and data on health checkups of the health insurance society held by JMDC Inc.. We constructed a machine learning model using the health checkup results, including sex and age, as explanatory variables and the outcome as the presence or absence of atrial fibrillation/flutter in insured persons (principals) aged 40-74 years 798,883 who underwent health checkups between January 1, 2005 and March 31, 2019. Area under the curve (AUC), which is an indicator of prediction accuracy, was 0.806 (95％confidence interval: 0.772-0.840). The top 10 important explanatory variables did not contradict the known risk of atrial fibrillation, such as sex, previous medical history (cardiovascular), and age, and the variable of ≥ 3 kg weight gain or loss over one year period was an independent risk factor. Moreover, AUC decreased to 0.804 in the model that excluded the relevant risk factors, which improved of prediction accuracy. The above findings showed that changes in yearly weight to the existing conduction criteria, as well as the model that we developed, may be useful for recommending ECG testing in specific health checkups.
The effect of magnetic field on the magnetic structure associated with magnetoelectric properties in a Y-type hexaferrite, Ba1.3Sr0.7CoZnFe11AlO22, was investigated by utilizing the soft x-ray ...resonant diffraction technique. In this hexaferrite, the so-called alternating longitudinal conical phase is stabilized at room temperature and zero magnetic field. Below room temperature, however, this phase is transformed into the so-called transverse conical phase by applying an in-plane magnetic field (≈ 0.3T). The transverse conical phase persists even after removing the magnetic field. The magnetoelectricity, which is magnetically-induced electric polarization, observed in the hexaferrite is discussed in terms of the temperature-dependent magnetic structure at zero field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
FGFR3 chondrodysplasia is caused by a gain-of-function mutation of the FGFR3 gene. The disease causes abnormal growth plate cartilage and lacks effective drug treatment. We sought to establish an ...in vivo model for the study of FGFR3 chondrodysplasia pathology and drug testing.
We created cartilage from human induced pluripotent stem cells (hiPSCs) and transplanted the cartilage into the subcutaneous spaces of immunodeficient mice. We then created cartilage from the hiPSCs of patients with FGFR3 chondrodysplasia and transplanted them into immunodeficient mice. We treated some mice with a FGFR inhibitor after the transplantation.
Xenografting the hiPSC-derived cartilage reproduced human growth plate cartilage consisting of zones of resting, proliferating, prehypertrophic and hypertrophic chondrocytes and bone in immunodeficient mice. Immunohistochemistry of xenografts using anti-human nuclear antigen antibody indicated that all chondrocytes in growth plate cartilage were human, whereas bone was composed of human and mouse cells. The pathology of small hypertrophic chondrocytes due to up-regulated FGFR3 signaling in FGFR3 skeletal dysplasia was recapitulated in growth plate cartilage formed in the xenografts of patient-specific hiPSC-derived cartilage. The mean diameters of hypertrophic chondrocytes between wild type and thanatophoric dysplasia were significantly different (95% CI: 13.2–26.9; n = 4 mice, one-way analysis of variance (ANOVA)). The pathology was corrected by systemic administration of a FGFR inhibitor to the mice.
The patient-specific growth plate cartilage xenograft model for FGFR3 skeletal dysplasia indicated recapitulation of pathology and effectiveness of a FGFR inhibitor for treatment and warrants more study for its usefulness to study disease pathology and drug testing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the ...structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood. In the PUFA-deprived mouse group, we observed lower motivation and higher sensitivity to a hallucinogenic drug resembling the prodromal symptoms in schizophrenia. Furthermore, a working-memory task-evoked hyper-neuronal activity in the medial prefrontal cortex was also observed, along with the downregulation of genes in the prefrontal cortex involved in oligodendrocyte integrity and the gamma-aminobutyric acid (GABA)-ergic system. Regulation of these genes was mediated by the nuclear receptor genes Rxr and Ppar, whose promoters were hyper-methylated by the deprivation of dietary AA and DHA. In addition, the RXR agonist bexarotene upregulated oligodendrocyte- and GABA-related gene expression and suppressed the sensitivity of mice to the hallucinogenic drug. Notably, the expression of these nuclear receptor genes were also downregulated in hair-follicle cells from schizophrenia patients. These results suggest that PUFA deficiency during the early neurodevelopmental period in mice could model the prodromal state of schizophrenia through changes in the epigenetic regulation of nuclear receptor genes.
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