Safety and efficacy assessment of standardized herbal formula PM012

<p>Abstract</p> <p>Background</p> <p>This study was conducted to evaluate the efficacy of the herbal formula PM012 on an Alzheimer's disease model, human presenilin 2 mutant transgenic mice (hPS2m), and also to evaluate the toxicity of PM012 in Sprague-Dawely rats after 4 or 26 weeks treatment with repeated oral administration.</p> <p>Methods</p> <p>Spatial learning and memory capacities of hPS2m transgenic mice were evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly administered orally to male and female SD rats (15/sex/group) at doses of 0 (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate the recovery potential, 5 animals of each sex were assigned to vehicle control and 2,000 mg/kg/day groups during the 4-week recovery period.</p> <p>Results</p> <p>The results showed that PM012-treated hPS2m transgenic mice showed significantly reduced escape latency when compared with the hPS2m transgenic mice. The repeated oral administration of PM012 over 26 weeks in male and female rats induced an increase and increasing trend in thymus weight in the female treatment groups (main and recovery groups), but the change was judged to be toxicologically insignificant. In addition, the oral administration of the herbal medicine PM012 did not cause adverse effects as assessed by clinical signs, mortality, body weight, food and water consumption, ophthalmology, urinalysis, hematology, serum biochemistry, blood clotting time, organ weights and histopathology. The No Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for both sexes, and the target organ was not identified.</p> <p>Conclusion</p> <p>These results suggest that PM012 has potential for use in the treatment of the Alzheimer's disease without serious adverse effects.</p

Probabilistic Phylogenetic Inference with Insertions and Deletions

A fundamental task in sequence analysis is to calculate the probability of a multiple alignment given a phylogenetic tree relating the sequences and an evolutionary model describing how sequences change over time. However, the most widely used phylogenetic models only account for residue substitution events. We describe a probabilistic model of a multiple sequence alignment that accounts for insertion and deletion events in addition to substitutions, given a phylogenetic tree, using a rate matrix augmented by the gap character. Starting from a continuous Markov process, we construct a non-reversible generative (birth–death) evolutionary model for insertions and deletions. The model assumes that insertion and deletion events occur one residue at a time. We apply this model to phylogenetic tree inference by extending the program dnaml in phylip. Using standard benchmarking methods on simulated data and a new “concordance test” benchmark on real ribosomal RNA alignments, we show that the extended program dnamlε improves accuracy relative to the usual approach of ignoring gaps, while retaining the computational efficiency of the Felsenstein peeling algorithm

DELVE-ing into the Jet: A Thin Stellar Stream on a Retrograde Orbit at 30 kpc

Abstract We perform a detailed photometric and astrometric analysis of stars in the Jet stream using data from the first data release of the DECam Local Volume Exploration Survey DR1 and Gaia EDR3. We discover that the stream extends over ∼ 29° on the sky (increasing the known length by 18°), which is comparable to the kinematically cold Phoenix, ATLAS, and GD-1 streams. Using blue horizontal branch stars, we resolve a distance gradient along the Jet stream of 0.2 kpc deg−1, with distances ranging from D ⊙ ∼ 27–34 kpc. We use natural splines to simultaneously fit the stream track, width, and intensity to quantitatively characterize density variations in the Jet stream, including a large gap, and identify substructure off the main track of the stream. Furthermore, we report the first measurement of the proper motion of the Jet stream and find that it is well aligned with the stream track, suggesting the stream has likely not been significantly perturbed perpendicular to the line of sight. Finally, we fit the stream with a dynamical model and find that it is on a retrograde orbit, and is well fit by a gravitational potential including the Milky Way and Large Magellanic Cloud. These results indicate the Jet stream is an excellent candidate for future studies with deeper photometry, astrometry, and spectroscopy to study the potential of the Milky Way and probe perturbations from baryonic and dark matter substructure.</jats:p

Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced Inflammatory Bowel Disease

<p>Abstract</p> <p>Background</p> <p>Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects of <it>Withania somnifera </it>in Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation.</p> <p>Methods</p> <p>The study included (i) preparation of gel formulation from aqueous <it>Withania somnifera </it>root extract (WSRE), (ii) biochemical assays to determine its performance potential, (iii) testing of formulation efficacy in TNBS-induced IBD rat model, and (iv) histo-patholgical studies to assess its healing and muco-regenerative effect in IBD-induced rats. For this purpose, concentration dependant antioxidant activity of the extracts were evaluated using biochemical assays like (a) inhibition of lipid peroxidation, (b) NO scavenging, (c) H₂O₂scavenging, and (d) ferric reducing power assay.</p> <p>Results</p> <p>The extract, at 500 μg/ml, the highest concentration tested, showed 95.6% inhibition of lipid peroxidation, 14.8% NO scavenging, 81.79% H₂O₂scavenging and a reducing capacity of 0.80. The results were comparable with standard antioxidants, ascorbic acid and curcumin. WSRE treatment positively scored on histopathological parameters like necrosis, edema, neutrophil infiltration. The post treatment intestinal features showed restoration at par with the healthy intestine. In view of these results, gel formulation containing an aqueous extract of <it>W. somnifera</it>, prepared for rectal application was tested for its anti-inflammatory activity in TNBS-induced rat models for IBD. Commercially available anti-inflammatory drug Mesalamine was used as the standard in this assay.</p> <p>Conclusions</p> <p>Dose of the rectal gel applied at 1000 mg of WSRE per kg rat weight showed significant muco-restorative efficacy in the IBD-induced rats, validated by histo-pathological studies.</p

Identification of Galaxy-Galaxy Strong Lens Candidates in the DECam Local Volume Exploration Survey Using Machine Learning

We perform a search for galaxy-galaxy strong lens systems using a convolutional neural network (CNN) applied to imaging data from the first public data release of the DECam Local Volume Exploration Survey, which contains 1/4520 million astronomical sources covering 1/44000 deg2 of the southern sky to a 5σ point-source depth of g = 24.3, r = 23.9, i = 23.3, and z = 22.8 mag. Following the methodology of similar searches using Dark Energy Camera data, we apply color and magnitude cuts to select a catalog of 1/411 million extended astronomical sources. After scoring with our CNN, the highest-scoring 50,000 images were visually inspected and assigned a score on a scale from 0 (not a lens) to 3 (very probable lens). We present a list of 581 strong lens candidates, 562 of which are previously unreported. We categorize our candidates using their human-assigned scores, resulting in 55 Grade A candidates, 149 Grade B candidates, and 377 Grade C candidates. We additionally highlight eight potential quadruply lensed quasars from this sample. Due to the location of our search footprint in the northern Galactic cap (b > 10 deg) and southern celestial hemisphere (decl. < 0 deg), our candidate list has little overlap with other existing ground-based searches. Where our search footprint does overlap with other searches, we find a significant number of high-quality candidates that were previously unidentified, indicating a degree of orthogonality in our methodology. We report properties of our candidates including apparent magnitude and Einstein radius estimated from the image separation

Increasing Potential Risk of a Global Aquatic Invader in Europe in Contrast to Other Continents under Future Climate Change

BACKGROUND: Anthropogenically-induced climate change can alter the current climatic habitat of non-native species and can have complex effects on potentially invasive species. Predictions of the potential distributions of invasive species under climate change will provide critical information for future conservation and management strategies. Aquatic ecosystems are particularly vulnerable to invasive species and climate change, but the effect of climate change on invasive species distributions has been rather neglected, especially for notorious global invaders. METHODOLOGY/PRINCIPAL FINDINGS: We used ecological niche models (ENMs) to assess the risks and opportunities that climate change presents for the red swamp crayfish (Procambarus clarkii), which is a worldwide aquatic invasive species. Linking the factors of climate, topography, habitat and human influence, we developed predictive models incorporating both native and non-native distribution data of the crayfish to identify present areas of potential distribution and project the effects of future climate change based on a consensus-forecast approach combining the CCCMA and HADCM3 climate models under two emission scenarios (A2a and B2a) by 2050. The minimum temperature from the coldest month, the human footprint and precipitation of the driest quarter contributed most to the species distribution models. Under both the A2a and B2a scenarios, P. clarkii shifted to higher latitudes in continents of both the northern and southern hemispheres. However, the effect of climate change varied considerately among continents with an expanding potential in Europe and contracting changes in others. CONCLUSIONS/SIGNIFICANCE: Our findings are the first to predict the impact of climate change on the future distribution of a globally invasive aquatic species. We confirmed the complexities of the likely effects of climate change on the potential distribution of globally invasive species, and it is extremely important to develop wide-ranging and effective control measures according to predicted geographical shifts and changes

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure

Study of production and cold nuclear matter effects in pPb collisions at=5 TeV

Production of mesons in proton-lead collisions at a nucleon-nucleon centre-of-mass energy = 5 TeV is studied with the LHCb detector. The analysis is based on a data sample corresponding to an integrated luminosity of 1.6 nb(-1). The mesons of transverse momenta up to 15 GeV/c are reconstructed in the dimuon decay mode. The rapidity coverage in the centre-of-mass system is 1.5 < y < 4.0 (forward region) and -5.0 < y < -2.5 (backward region). The forward-backward production ratio and the nuclear modification factor for (1S) mesons are determined. The data are compatible with the predictions for a suppression of (1S) production with respect to proton-proton collisions in the forward region, and an enhancement in the backward region. The suppression is found to be smaller than in the case of prompt J/psi mesons

Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]&lt;2.20(2.56) and Γ[Ξb(6333)0]&lt;1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances