Prospects for high-resolution microwave spectroscopy of methanol in a Stark-deflected molecular beam

Recently, the extremely sensitive torsion-rotation transitions in methanol have been used to set a tight constraint on a possible variation of the proton-to-electron mass ratio over cosmological time scales. In order to improve this constraint, laboratory data of increased accuracy will be required. Here, we explore the possibility for performing high-resolution spectroscopy on methanol in a Stark-deflected molecular beam. We have calculated the Stark shift of the lower rotational levels in the ground torsion-vibrational state of CH3OH and CD3OH molecules, and have used this to simulate trajectories through a typical molecular beam resonance setup. Furthermore, we have determined the efficiency of non-resonant multi-photon ionization of methanol molecules using a femtosecond laser pulse. The described setup is in principle suited to measure microwave transitions in CH3OH at an accuracy below 10^{-8}

Left atrial thrombus resolution in atrial fibrillation or flutter:Results of a prospective study with rivaroxaban (X-TRA) and a retrospective observational registry providing baseline data (CLOT-AF)

BackgroundData on left atrial/left atrial appendage (LA/LAA) thrombus resolution after non–vitamin K antagonist (VKA) oral anticoagulant treatment are scarce. The primary objective of X-TRA was to explore the use of rivaroxaban for the resolution of LA/LAA thrombi in patients with nonvalvular atrial fibrillation (AF) or atrial flutter, with the CLOT-AF registry providing retrospective data after standard-of-care therapy in this setting.MethodsX-TRA was a prospective, single-arm, open-label, multicenter study that investigated rivaroxaban treatment for 6 weeks for LA/LAA thrombus resolution in patients with nonvalvular AF or atrial flutter and LA/LAA thrombus confirmed at baseline on a transesophageal echocardiogram (TEE). CLOT-AF retrospectively collected thrombus-related patient outcome data after standard-of-care anticoagulant treatment for 3 to 12 weeks in patients with nonvalvular AF or atrial flutter who had LA/LAA thrombi on TEE recorded in their medical file.ResultsIn X-TRA, patients were predominantly (95.0%) from Eastern European countries. The adjudicated thrombus resolution rate was 41.5% (22/53 modified intention-to-treat [mITT] patients, 95% CI 28.1%-55.9%) based on central TEE assessments. Resolved or reduced thrombus was evident in 60.4% (32/53 mITT patients, 95% CI 46.0%-73.6%) of patients. In CLOT-AF, the reported thrombus resolution rate was 62.5% (60/96 mITT patients, 95% CI 52.0%-72.2%) and appeared better in Western European countries (34/50; 68.0%) than in Eastern European countries (26/46; 56.5%).ConclusionX-TRA is the first prospective, multicenter study examining LA/LAA thrombus resolution with a non-VKA oral anticoagulant in VKA-naïve patients or in patients with suboptimal VKA therapy. Rivaroxaban could be a potential option for the treatment of LA/LAA thrombi

The acetyltransferase p300 is recruited in trans to multiple enhancer sites by lncSmad7

The histone acetyltransferase p300 (also known as KAT3B) is a general transcriptional coactivator that introduces the H3K27ac mark on enhancers triggering their activation and gene transcription. Genome-wide screenings demonstrated that a large fraction of long non-coding RNAs (lncRNAs) plays a role in cellular processes and organ development although the underlying molecular mechanisms remain largely unclear (1,2). We found 122 lncRNAs that interacts directly with p300. In depth analysis of one of these, lncSmad7, is required to maintain ESC self-renewal and it interacts to the C-terminal domain of p300. lncSmad7 also contains predicted RNA-DNA Hoogsteen forming base pairing. Combined Chromatin Isolation by RNA precipitation followed by sequencing (ChIRP-seq) together with CRISPR/Cas9 mutagenesis of the target sites demonstrate that lncSmad7 binds and recruits p300 to enhancers in trans, to trigger enhancer acetylation and transcriptional activation of its target genes. Thus, these results unveil a new mechanism by which p300 is recruited to the genome

Influence of Social and Behavioural Characteristics of Users on Their Evaluation of Subjective Loudness and Acoustic Comfort in Shopping Malls

A large-scale subjective survey was conducted in six shopping malls in Harbin City, China, to determine the influence of social and behavioural characteristics of users on their evaluation of subjective loudness and acoustic comfort. The analysis of social characteristics shows that evaluation of subjective loudness is influenced by income and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Meanwhile, evaluation of acoustic comfort evaluation is influenced by income, education level, and occupation, with correlation coefficients or contingency coefficients of 0.10 to 0.60 (p<0.05 or p<0.01). The effect of gender and age on evaluation of subjective loudness and acoustic comfort is statistically insignificant. The effects of occupation are mainly caused by the differences in income and education level, in which the effects of income are greater than that of education level. In terms of behavioural characteristics, evaluation of subjective loudness is influenced by the reason for visit, frequency of visit, and length of stay, with correlation coefficients or contingency coefficients of 0.10 to 0.40 (p<0.05 or p<0.01). Evaluation of acoustic comfort is influenced by the reason for visit to the site, the frequency of visit, length of stay, and also season of visit, with correlation coefficients of 0.10 to 0.30 (p<0.05 or p<0.01). In particular, users who are waiting for someone show lower evaluation of acoustic comfort, whereas users who go to shopping malls more than once a month show higher evaluation of acoustic comfort. On the contrary, the influence of the period of visit and the accompanying persons are found insignificant

Macrophage IL-1β contributes to tumorigenesis through paracrine AIM2 inflammasome activation in the tumor microenvironment

Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1β production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1β enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer