We report the discovery of a giant planet in the OGLE-2017-BLG-1522 microlensing event. The planetary perturbations were clearly identified by high-cadence survey experiments despite the relatively ...short event timescale of tE ∼ 7.5 days. The Einstein radius is unusually small, θE = 0.065 mas, implying that the lens system either has very low mass or lies much closer to the microlensed source than the Sun, or both. A Bayesian analysis yields component masses and source-lens distance , implying that this is a brown-dwarf/Jupiter system that probably lies in the Galactic bulge, a location that is also consistent with the relatively low lens-source relative proper motion = 3.2 0.5 mas yr−1. The projected companion-host separation is , indicating that the planet is placed beyond the snow line of the host, i.e., asl ∼ 0.12 au. Planet formation scenarios combined with the small companion-host mass ratio q ∼ 0.016 and separation suggest that the companion could be the first discovery of a giant planet that formed in a protoplanetary disk around a brown-dwarf host.
Histone deacetylase (HDAC) inhibitors (HDIs) are promising anticancer therapies and have been clinically used for the treatment of hematological malignancy. However, their efficacy in solid tumors is ...marginal and drug resistance hampers their further clinical utility. To develop novel strategies for the HDI-based anticancer therapeutics in non-small cell lung cancer (NSCLC), in the present study, we investigated the mechanisms underlying resistance to HDI treatment in NSCLC cells. We show the STAT3-mediated IGF2/IGF-1R signaling cascade as a key modulator for both acquired and primary HDI resistance. The treatment with HDI upregulated IGF2 transcription in NSCLC cells carrying intrinsic or acquired drug resistance via direct binding of STAT3 in IGF2 P3 and P4 promoters. Acetylated STAT3 emerged upon HDAC inhibition was protected from the proteasome-mediated degradation of STAT3 and functioned as a direct transcription factor for IGF2 expression. Genomic or pharmacological strategies targeting STAT3 diminished the HDI-induced IGF2 mRNA expression and overcame the resistance to HDI treatment in HDI-resistant NSCLC- or patient-derived tumor xenograft models. These findings provide new insights into the role of acetylated STAT3-mediated activation of IGF2 transcription in HDI resistance, suggesting IGF2 or STAT3 as novel targets to overcome HDI resistance in NSCLC.
Current microlensing surveys are sensitive to free-floating planets down to Earth-mass objects. All published microlensing events attributed to unbound planets were identified based on their short ...timescale (below two days), but lacked an angular Einstein radius measurement (and hence lacked a significant constraint on the lens mass). Here, we present the discovery of a Neptune-mass free-floating planet candidate in the ultrashort (tE = 0.320 0.003 days) microlensing event OGLE-2016-BLG-1540. The event exhibited strong finite-source effects, which allowed us to measure its angular Einstein radius of θE = 9.2 0.5 as. There remains, however, a degeneracy between the lens mass and distance. The combination of the source proper motion and source-lens relative proper motion measurements favors a Neptune-mass lens located in the Galactic disk. However, we cannot rule out that the lens is a Saturn-mass object belonging to the bulge population. We exclude stellar companions up to ∼15 au.
Background and purpose
To clarify whether subtyping of amnestic and non‐amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of ...neuroimaging and longitudinal cognitive changes.
Methods
We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting‐state functional connectivity between the patients with de‐novo PD with amnestic MCI (PD‐aMCI) (n = 50) and non‐amnestic MCI (PD‐naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de‐novo PD‐aMCI (n = 125) and PD‐naMCI (n = 61).
Results
The demographic data showed that scores in memory domains were lower in the PD‐aMCI group compared with the PD‐naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD‐aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD‐aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD‐naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD‐aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD‐naMCI (P = 0.022). In addition, the PD‐aMCI group had a higher risk of dementia conversion than the PD‐naMCI group.
Conclusions
This study suggests that the designation of PD‐MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.
International Consensus on drug allergy Demoly, P.; Adkinson, N. F.; Brockow, K. ...
Allergy,
April 2014, Letnik:
69, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug‐specific antibodies or T cells. DHRs may be allergic or ...nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life‐threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under‐reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more‐expensive or less‐effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class‐induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of DHRs.
We present a background model for dark matter searches using an array of NaI(Tl) crystals in the COSINE-100 experiment that is located in the Yangyang underground laboratory. The model includes ...background contributions from both internal and external sources, including cosmogenic radionuclides and surface
210
Pb contamination. To build the model in the low energy region, with a threshold of 1 keV, we used a depth profile of
210
Pb contamination in the surface of the NaI(Tl) crystals determined in a comparison between measured and simulated spectra. We also considered the effect of the energy scale errors propagated from the statistical uncertainties and the nonlinear detector response at low energies. The 1.7 years COSINE-100 data taken between October 21, 2016 and July 18, 2018 were used for this analysis. Our Monte Carlo simulation provides a non-Gaussian peak around 50 keV originating from beta decays of bulk
210
Pb in a good agreement with the measured background. This model estimates that the activities of bulk
210
Pb and
3
H are dominating the background rate that amounts to an average level of
2.85
±
0.15
counts/day/keV/kg in the energy region of (1–6) keV, using COSINE-100 data with a total exposure of 97.7 kg
·
years.
We report two microlensing events, KMT-2017-BLG-1038 and KMT-2017-BLG-1146, that are caused by planetary systems. These events were discovered by Korea Microlensing Telescope Network survey ...observations from the 2017 bulge season. The discovered systems consist of a planet and host star with mass ratios of and , respectively. Based on a Bayesian analysis assuming a Galactic model without stellar remnant hosts, we find that the planet KMT-2017-BLG-1038Lb is a super-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) that is located at kpc toward the Galactic bulge. The other planet, KMT-2017-BLG-1146Lb, is a sub-Jupiter-mass planet ( ) orbiting a mid-M dwarf host ( ) at a distance of kpc toward the Galactic bulge. Both are potentially gaseous planets that are beyond their hosts' snow lines. These typical microlensing planets will be routinely discovered by second-generation microlensing surveys, rapidly increasing the number of detections.
On 6 March 2015, Dawn arrived at Ceres to find a dark, desiccated surface punctuated by small, bright areas. Parts of Ceres' surface are heavily cratered, but the largest expected craters are absent. ...Ceres appears gravitationally relaxed at only the longest wavelengths, implying a mechanically strong lithosphere with a weaker deep interior. Ceres' dry exterior displays hydroxylated silicates, including ammoniated clays of endogenous origin. The possibility of abundant volatiles at depth is supported by geomorphologie features such as flat crater floors with pits, lobate flows of materials, and a singular mountain that appears to be an extrusive cryovolcanic dome. On one occasion, Ceres temporarily interacted with the solar wind, producing a bow shock accelerating electrons to energies of tens of kilovolts.
The aim of the present study was to elucidate the fundamental mechanism of bovine oviduct epithelial cell (BOEC) co‐culture on developmental capacity of bovine in vitro oocyte maturation/in vitro ...fertilization (IVM/IVF) embryos. We examined the effects of astaxanthin against nitric oxide‐induced oxidative stress on cell viability by MTT assay, lipid peroxidation (LPO) by using thiobarbituric acid (TBA) reaction for malondialdehyde (MDA) and the expression of antioxidant genes (CuZnSOD, MnSOD and Catalase) or apoptosis genes (Bcl‐2, Caspase‐3 and Bax) by RT‐PCR in BOEC. We also evaluated the developmental rates of bovine IVM/IVF embryos co‐cultured with BOEC pre‐treated with astaxanthin (500 μm) in the presence or absence of sodium nitroprusside (SNP, 1000 μm) for 24 h. Cell viability in BOEC treated with SNP (50-2000 μm) lowered, while astaxanthin addition (50-500 μm) increased it in a dose‐dependent manner. Cell viability in astaxanthin plus SNP (1000 μm) gradually recovered according to the increase in astaxanthin additions (100-500 mm). The LPO in astaxanthin group (50-500 μM) gradually decreased in a dose dependent manner and among SNP or astaxanthin plus SNP group, SNP alone and astaxanthin (50 μM) plus SNP shown a significant increase than other groups (p < 0.05). Expression of apoptosis or antioxidant genes was detected by RT‐PCR. Bcl‐2 and antioxidant genes were detected in astaxanthin or astaxanthin plus SNP group, and Caspase‐3 and Bax genes were only found in SNP group. When bovine IVM/IVF embryos were cultured for 6-7 days under co‐culture system such as BOEC treated with astaxanthin in the presence or absence of SNP, the developmental ability to blastocysts in 500 μm astaxanthin group was the highest of all groups. These results suggest that astaxanthin has a antioxidative effect on cell viability and LPO of BOEC, and development of bovine IVM/IVF embryos due to the induction of antioxidant genes and suppression of apoptosis genes.
Microorganisms such as fungi and bacteria cause many human diseases and therefore rapid and accurate identification of these substances is essential for effective treatment and prevention of further ...infections. In particular, contemporary microbial detection technique is limited by the low detection speed which usually extends over a couple of days. Here we demonstrate that metamaterials operating in the terahertz frequency range shows promising potential for use in fabricating the highly sensitive and selective microbial sensors that are capable of high-speed on-site detection of microorganisms in both ambient and aqueous environments. We were able to detect extremely small amounts of the microorganisms, because their sizes are on the same scale as the micro-gaps of the terahertz metamaterials. The resonant frequency shift of the metamaterials was investigated in terms of the number density and the dielectric constants of the microorganisms, which was successfully interpreted by the change in the effective dielectric constant of a gap area.
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