Miracle-dz/UniFAR-FTUs huggingface dataset:
Rayleigh/Raman lidar observations of gravity wave activity from 15 to 70 km altitude over Syowa (69°S, 40°E), the Antarctic

The potential energy of gravity waves (GWs) per unit mass (Ep), at altitudes of 15–70 km, has been examined from temperature profiles obtained by a Rayleigh/Raman lidar at Syowa Station (69°S, 40°E) from May 2011 to October 2013, with the exception of the summer months. The GWs with ground‐based wave periods longer than 2 h and vertical wavelengths between 1.8 and 16 km were extracted from the temperature profiles. Ep was larger in winter than in spring and fall, although in 2012, at altitudes below 30 km, Ep was larger in spring than in winter and fall. Ep increased with a mean scale height of 11.3 km. Ep profiles showed a local maximum at an altitude of 20 km and a minimum at 25 km in almost every month, which has not been reported by previous studies observed by radiosondes. The values of Ep in October of 2012 were smaller at 35–60 km and larger at 20–35 km than those in October of 2011 and 2013. This difference in the Ep profile is most probably caused by different seasonal variations of zonal winds. The larger and smaller Ep values seem to be observed both below and above the altitude at which the zonal wind speed reached 0 m s−1. This result suggests that wind filtering of gravity waves with small phase speeds is significantly important in early spring.
DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice.

Background Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW264.7 cells. Results DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.
1 Should We Be Thinking about Robot Sex

There is a cave in the Swabian Alps in Germany. It is called the Hohle Fels (rough translation “hollow rock”). Archaeologists have been excavating it since the late 1800s and have discovered there a number of important artifacts from the Upper Paleolithic era. In June 2005, they announced a particularly interesting discovery. They announced that they had unearthed the world's oldest dildo.
Online and offline effects of parietal 10 Hz repetitive transcranial magnetic stimulation on working memory in healthy controls

Abstract Parietal alpha activity shows a specific pattern of phasic changes during working memory. It decreases during the encoding and recall phases but increases during the maintenance phase. This study tested whether online rTMS delivered to the parietal cortex during the maintenance phase of a working memory task would increase alpha activity and hence improve working memory. Then, 46 healthy volunteers were randomly assigned to two groups to receive 3‐day parietal 10 Hz online rTMS (either real or sham, 3600 pulses in total) that were time‐locked to the maintenance phase of a spatial span task (180 trials in total). Behavioral performance on another spatial span task and EEG signals during a change detection task were recorded on the day before the first rTMS (pretest) and the day after the last rTMS (posttest). We found that rTMS improved performance on both online and offline spatial span tasks. For the offline change detection task, rTMS enhanced alpha activity within the maintenance phase and improved interference control of working memory at both behavioral (K score) and neural (contralateral delay activity) levels. These results suggested that rTMS with alpha frequency time‐locked to the maintenance phase is a promising way to boost working memory.
Engineering of Cas12a nuclease variants with enhanced genome-editing specificity

The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-As retains on-target activities comparable to wild-type AsCas12a (AsCas12aWT) in human cells. We demonstrated that HyperFi-As has dramatically reduced off-target effects in human cells, and HyperFi-As possessed notably a lower tolerance to mismatch at the position of the PAM-distal region compared with the wild type. Further, a modified single-molecule DNA unzipping assay at proper constant force was applied to evaluate the stability and transient stages of the CRISPR/Cas ribonucleoprotein (RNP) complex. Multiple states were sensitively detected during the disassembly of the DNA-Cas12a-crRNA complexes. On off-target DNA substrates, the HyperFi-As-crRNA was harder to maintain the R-loop complex state compared to the AsCas12aWT, which could explain exactly why the HyperFi-As has low off-targeting effects in human cells. Our findings provide a novel version of AsCas12a variant with low off-target effects, especially capable of dealing with the high off-targeting in the distal region from the PAM. An insight into how the AsCas12a variant behaves at off-target sites was also revealed at the single-molecule level and the unzipping assay to evaluate multiple states of CRISPR/Cas RNP complexes might be greatly helpful for a deep understanding of how CRISPR/Cas behaves and how to engineer it in future.
Estimation of Altitude in Stereoscopic-3D Versus 2D Real-world Scenes

Research on the role of human stereopsis has largely focused on laboratory studies that control or eliminate other cues to depth. However, in everyday environments we rarely rely on a single source of depth information. Despite this, few studies have assessed the impact of binocular vision on depth judgements in real-world scenarios presented in simulation. Here we conducted a series of experiments to determine if, and to what extent, stereoscopic depth provides a benefit for tasks commonly performed by helicopter aircrew. We assessed the impact of binocular vision and stereopsis on perception of (1) relative and (2) absolute distance above the ground (altitude) using natural and simulated stereoscopic-3D (S3D) imagery. The results showed that, consistent with the literature, binocular vision provides very weak input to absolute altitude estimates at high altitudes (10-100ft). In contrast, estimates of relative altitude at low altitudes (0-5ft) were critically dependent on stereopsis, irrespective of terrain type. These findings are consistent with the view that stereopsis provides important information for altitude judgments when close to the ground; while at high altitudes these judgments are based primarily on the perception of 2D cues.
Lost in space(s): Multimodal neuroimaging of disorientation along the Alzheimer's disease continuum

Abstract Orientation is a fundamental cognitive faculty and the bedrock of the neurologic examination. Orientation is defined as the alignment between an individual's internal representation and the external world in the spatial, temporal, and social domains. While spatial disorientation is a recognized hallmark of Alzheimer's disease (AD), little is known about disorientation beyond space in AD. This study aimed to explore disorientation in spatial, temporal, and social domains along the AD continuum. Fifty‐one participants along the AD continuum performed an ecological orientation task in the spatial, temporal, and social domains while undergoing functional MRI. Disorientation in AD followed a three‐way association between orientation domain, brain region, and disease stage. Specifically, patients with early amnestic mild cognitive impairment exhibited spatio‐temporal disorientation and reduced brain activity in temporoparietal regions, while patients with AD dementia showed additional social disorientation and reduced brain activity in frontoparietal regions. Furthermore, patterns of hypoactivation overlapped different subnetworks of the default mode network, patterns of fluorodeoxyglucose hypometabolism, and cortical atrophy characteristic of AD. Our results suggest that AD may encompass a disorder of orientation, characterized by a biphasic process manifesting as early spatio‐temporal and late social disorientation. As such, disorientation may offer a unique window into the clinicopathological progression of AD. Significance statement Despite extensive research into Alzheimer's disease (AD), its core cognitive deficit remains a matter of debate. In this study, we investigated whether orientation, defined as the ability to align internal representations with the external world in spatial, temporal, and social domains, constitutes a core cognitive deficit in AD. To do so, we used PET‐fMRI imaging to collect behavioral, functional, and metabolic data from 51 participants along the AD continuum. Our findings suggest that AD may constitute a disorder of orientation, characterized by an early spatio‐temporal disorientation and followed by late social disorientation, manifesting in task‐evoked and neurodegenerative changes. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD and as such could greatly benefit disease diagnosis, monitoring, and evaluation of treatment response.
Saffron therapy for the ongoing treatment of age-related macular degeneration

Objective To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). Methods and analysis Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption. Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these. Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. Results At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3–6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1–6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. Conclusion Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.
Heterochromatin in plant meiosis

ABSTRACT Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I.
Diabetes: treating hypertension.

INTRODUCTION Between 2007 and 2010, the age-adjusted prevalence of hypertension in US adults with diabetes was 59%, more than double the prevalence in those without diabetes. Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical question: What are the effects of different blood pressure targets in people with diabetes and hypertension? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 10 studies that met our inclusion criteria. CONCLUSIONS In this systematic review, we present information relating to the effectiveness and safety of the following intervention: more intensive (lower) blood pressure targets versus less intensive (higher) targets in people with diabetes and hypertension.
Evidence of Nonrandom Patterns of Functional Chromosome Organization in Danaus plexippus

Abstract Our understanding on the interplay between gene functionality and gene arrangement at different chromosome scales relies on a few Diptera and the honeybee, species with quality reference genome assemblies, accurate gene annotations, and abundant transcriptome data. Using recently generated ‘omic resources in the monarch butterfly Danaus plexippus, a species with many more and smaller chromosomes relative to Drosophila species and the honeybee, we examined the organization of genes preferentially expressed at broadly defined developmental stages (larva, pupa, adult males, and adult females) at both fine and whole-chromosome scales. We found that developmental stage–regulated genes do not form more clusters, but do form larger clusters, than expected by chance, a pattern consistent across the gene categories examined. Notably, out of the 30 chromosomes in the monarch genome, 12 of them, plus the fraction of the chromosome Z that corresponds to the ancestral Z in other Lepidoptera, were found enriched for developmental stage–regulated genes. These two levels of nonrandom gene organization are not independent as enriched chromosomes for developmental stage–regulated genes tend to harbor disproportionately large clusters of these genes. Further, although paralogous genes were overrepresented in gene clusters, their presence is not enough to explain two-thirds of the documented cases of whole-chromosome enrichment. The composition of the largest clusters often included paralogs from more than one multigene family as well as unrelated single-copy genes. Our results reveal intriguing patterns at the whole-chromosome scale in D. plexippus while shedding light on the interplay between gene expression and chromosome organization beyond Diptera and Hymenoptera.
Vertical Profile of PAHs and Dredging Depth of River Sediments

Abstract Sediment dredging is an effective engineering measure to reduce the negative effects of PAHs pollution on water environment. The dredging depth is a key parameter in environmental dredging engineering. A guidance of environmental dredging depth needed to reduce the toxicity risk was developed which was specifically designed for the removal of river sediments contaminated by PAHs based on the mean effect range median quotients (mean-ERM-q). The dredging depths for removing river sediments were calculated based on the vertical profile of PAHs content and the quality guidelines of sediment. Pinghu water system was carried out to determine the dredging depths of sediments from nine rivers by the proposed method. Each sediment core was collected from different river. The results showed the profiles of PAHs in sediment cores were irregular and diverse due to river dredging events and human activities in different periods. The risk assessment of PAHs toxicity showed one of nine cores with moderate-high probability, 4 of nine cores with low-moderate probability and the others with low toxicity risk. The achievement can offer a reference to the dredging engineering in other similar river systems.
Uncovering a hidden functional role of the XRE-cupin protein PsdR as a novel quorum-sensing regulator in Pseudomonas aeruginosa

XRE-cupin family proteins containing an DNA-binding domain and a cupin signal-sensing domain are widely distributed in bacteria. In Pseudomonas aeruginosa, XRE-cupin transcription factors have long been recognized as regulators exclusively controlling cellular metabolism pathways. However, their potential functional roles beyond metabolism regulation remain unknown. PsdR, a typical XRE-cupin transcriptional regulator, was previously characterized as a local repressor involved solely in dipeptide metabolism. Here, by measuring quorum-sensing (QS) activities and QS-controlled metabolites, we uncover that PsdR is a new QS regulator in P. aeruginosa. Our RNA-seq analysis showed that rather than a local regulator, PsdR controls a large regulon, including genes associated with both the QS circuit and non-QS pathways. To unveil the underlying mechanism of PsdR in modulating QS, we developed a comparative transcriptome approach named “transcriptome profile similarity analysis” (TPSA). Using this TPSA method, we revealed that PsdR expression causes a QS-null-like transcriptome profile, resulting in QS-inactive phenotypes. Based on the results of TPSA, we further demonstrate that PsdR directly binds to the promoter for the gene encoding the QS master transcription factor LasR, thereby negatively regulating its expression and influencing QS activation. Moreover, our results showed that PsdR functions as a negative virulence regulator, as inactivation of PsdR enhanced bacterial cytotoxicity on host cells. In conclusion, we report on a new QS regulation role for PsdR, providing insights into its role in manipulating QS-controlled virulence. Most importantly, our findings open the door for a further discovery of untapped functions for other XRE-Cupin family proteins.
Prevalence of abnormal left ventricular global longitudinal strain by speckle tracking echocardiography and its prognostic value in patients with COVID-19

Importance Although cardiac injury is a known complication of COVID-19 infection, there is no established tool to predict cardiac involvement and in-hospital mortality in this patient population. Objective To assess if left ventricular global longitudinal strain (LV-GLS) can detect cardiac involvement and be used as a risk-stratifying parameter for hospitalised patients with COVID-19. Main outcomes and measures In-hospital mortality. Results We found a statistically significant association between LV-GLS and in-hospital mortality (adjusted OR (aOR)=1.09; 95% CI 1.0 to 1.19, p=0.050). Furthermore, right ventricular fractional area change was significantly associated with in-hospital mortality (aOR=1.04; 95% CI 1.0 to 1.08, p=0.043). Troponin level had no statistically significant association with in-hospital mortality (aOR=3.43; 95% CI 0.78 to 15.03, p=0.101). Conclusion and relevance LV-GLS can be a useful parameter for cardiovascular risk assessment in hospitalised patients with COVID-19 infection.
Acetazolamide Challenge Changes Outer Retina Bioenergy-Linked and Anatomical OCT Biomarkers Depending on Mouse Strain

Purpose The purpose of this study was to test the hypothesis that optical coherence tomography (OCT) bioenergy-linked and anatomical biomarkers are responsive to an acetazolamide (ACZ) provocation. Methods C57BL/6J mice (B6J, a strain with relatively inefficient mitochondria) and 129S6/ev mice (S6, a strain with relatively efficient mitochondria) were given a single IP injection of ACZ (carbonic anhydrase inhibitor) or vehicle. In each mouse, the Mitochondrial Configuration within Photoreceptors based on the profile shape Aspect Ratio (MCP/AR) index was determined from the hyper-reflective band immediately posterior to the external limiting membrane (ELM). In addition, we tested for ACZ-induced acidification by measuring contraction of the external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness; the hyporeflective band (HB) signal intensity at the photoreceptor tips was also examined. Finally, the nuclear layer thickness was measured. Results In response to ACZ, MCP/AR was greater-than-vehicle in B6J mice and lower-than-vehicle in S6 mice. ACZ-treated B6J and S6 mice both showed ELM-RPE contraction compared to vehicle-treated mice, consistent with dehydration in response to subretinal space acidification. The HB intensity at the photoreceptor tips and the outer nuclear layer thickness (B6J and S6), as well as the inner nuclear layer thickness of B6J mice, were all lower than vehicle following ACZ. Conclusions Photoreceptor respiratory efficacy can be evaluated in vivo based on distinct rod mitochondria responses to subretinal space acidification measured with OCT biomarkers and an ACZ challenge, supporting and extending our previous findings measured with light-dark conditions.
Arctic sea ice response to the eruptions of Agung, El Chichón, and Pinatubo

Using a large initial condition ensemble of climate model simulations, we examine the impact of volcanic activity on Arctic sea ice cover from 1960 to 2005, a period that includes three very large tropical eruptions. Ensemble averaging across simulations with natural (volcanic and solar) forcings alone reduces noise due to internal variability to show a decade of increased Arctic sea extent (of up to half a million square kilometers) following each of the Mount Agung (1963), Mount El Chichón (1982), and Mount Pinatubo (1991) eruptions. A similar impact is seen when averaging over a large ensemble of simulations with natural and all‐known anthropogenic forcings. We show that the volcanic response in sea ice cover is sensitive to preeruption temperature, with warmer conditions before an eruption being associated with a larger than average response. Finally, a detection and attribution analysis using second‐generation Canadian Earth System Model (CanESM2) did not identify a significant response in the observations, while finding no evidence of inconsistency between observations and CanESM2 since regression coefficients were consistent with unity. A similar detection and attribution analysis using the somewhat stronger volcanic response from the simulations in the average of the CMIP5 models did identify a detectable natural forcing response in four observational sea ice extent data sets.