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

Enriching a biomedical event corpus with meta-knowledge annotation

Background: Biomedical papers contain rich information about entities, facts and events of biological relevance. To discover these automatically, we use text mining techniques, which rely on annotated corpora for training. In order to extract protein-protein interactions, genotype-phenotype/gene-disease associations, etc., we rely on event corpora that are annotated with classified, structured representations of important facts and findings contained within text. These provide an important resource for the training of domain-specific information extraction (IE) systems, to facilitate semantic-based searching of documents. Correct interpretation of these events is not possible without additional information, e.g., does an event describe a fact, a hypothesis, an experimental result or an analysis of results? How confident is the author about the validity of her analyses? These and other types of information, which we collectively term meta-knowledge, can be derived from the context of the event.Results: We have designed an annotation scheme for meta-knowledge enrichment of biomedical event corpora. The scheme is multi-dimensional, in that each event is annotated for 5 different aspects of meta-knowledge that can be derived from the textual context of the event. Textual clues used to determine the values are also annotated. The scheme is intended to be general enough to allow integration with different types of bio-event annotation, whilst being detailed enough to capture important subtleties in the nature of the meta-knowledge expressed in the text. We report here on both the main features of the annotation scheme, as well as its application to the GENIA event corpus (1000 abstracts with 36,858 events). High levels of inter-annotator agreement have been achieved, falling in the range of 0.84-0.93 Kappa.Conclusion: By augmenting event annotations with meta-knowledge, more sophisticated IE systems can be trained, which allow interpretative information to be specified as part of the search criteria. This can assist in a number of important tasks, e.g., finding new experimental knowledge to facilitate database curation, enabling textual inference to detect entailments and contradictions, etc. To our knowledge, our scheme is unique within the field with regards to the diversity of meta-knowledge aspects annotated for each event. © 2011 Thompson et al; licensee BioMed Central Ltd

Layered BiOI single crystals capable of detecting low dose rates of X-rays.

Detecting low dose rates of X-rays is critical for making safer radiology instruments, but is limited by the absorber materials available. Here, we develop bismuth oxyiodide (BiOI) single crystals into effective X-ray detectors. BiOI features complex lattice dynamics, owing to the ionic character of the lattice and weak van der Waals interactions between layers. Through use of ultrafast spectroscopy, first-principles computations and detailed optical and structural characterisation, we show that photoexcited charge-carriers in BiOI couple to intralayer breathing phonon modes, forming large polarons, thus enabling longer drift lengths for the photoexcited carriers than would be expected if self-trapping occurred. This, combined with the low and stable dark currents and high linear X-ray attenuation coefficients, leads to strong detector performance. High sensitivities reaching 1.1  × 103 μC Gyair-1 cm-2 are achieved, and the lowest dose rate directly measured by the detectors was 22 nGyair s-1. The photophysical principles discussed herein offer new design avenues for novel materials with heavy elements and low-dimensional electronic structures for (opto)electronic applications

Layered BiOI single crystals capable of detecting low dose rates of X-rays.

Detecting low dose rates of X-rays is critical for making safer radiology instruments, but is limited by the absorber materials available. Here, we develop bismuth oxyiodide (BiOI) single crystals into effective X-ray detectors. BiOI features complex lattice dynamics, owing to the ionic character of the lattice and weak van der Waals interactions between layers. Through use of ultrafast spectroscopy, first-principles computations and detailed optical and structural characterisation, we show that photoexcited charge-carriers in BiOI couple to intralayer breathing phonon modes, forming large polarons, thus enabling longer drift lengths for the photoexcited carriers than would be expected if self-trapping occurred. This, combined with the low and stable dark currents and high linear X-ray attenuation coefficients, leads to strong detector performance. High sensitivities reaching 1.1  × 103 μC Gyair-1 cm-2 are achieved, and the lowest dose rate directly measured by the detectors was 22 nGyair s-1. The photophysical principles discussed herein offer new design avenues for novel materials with heavy elements and low-dimensional electronic structures for (opto)electronic applications

Layered BiOI single crystals capable of detecting low dose rates of X-rays

Acknowledgements: We would like to thank Prof. Richard Phillips (University of Cambridge) for useful feedback on the manuscript and help with optical measurements. The authors also thank Zhuotong (Thomas) Sun (University of Cambridge) for assistance on the powder X-ray diffraction measurements, and Prof. James Marrow and Marcus Williamson (University of Oxford) for assistance in taking radiographs. R.A.J. acknowledges funding from an EPSRC Department Training Partnership studentship (no. EP/N509620/1), as well as Bill Welland and the Winton Programme for the Physics of Sustainability. L.E. and T.V.D.G. acknowledge support from the EPSRC Cambridge NanoDTC (no. EP/L015978/1). L.E. acknowledges funding by the DFG (project no. 387651688). T.V.D.G. also acknowledges financial support from the Schiff Foundation. K.G. and S.D.S. acknowledge the EPSRC (no. EP/R023980/1) for funding. S.D.S. acknowledges the Royal Society and Tata Group (no. UF150033) and EPSRC (no. EP/W004445/1) for funding. The work has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (HYPERION - grant agreement no. 756962; PEROVSCI - 957513). The work was supported by a Royal Society International Exchanges Cost Share award (no. IEC\R2\170108) and the Alliance Hubert Curien Programme of the British Council (no. 608412749). K.R.D. thanks the Department of Chemistry at the University of Oxford for a studentship. P.P. appreciates support from National Science Centre Poland within the OPUS program (no. 2019/33/B/ST3/01915). This work was partially supported by OPEP project, which received funding from the ANR-10-LABX-0037-NEXT. The Polish participation in European Magnetic Field Laboratory is supported by the DIR/WK/2018/07 grant from Ministry of Science and Higher Education, Poland. F.D. acknowledges support from the DFG Emmy Noether Programme (project no. 387651688) and the Winton Programme for the Physics of Sustainability. J.L.M.-D. acknowledges funding from the Royal Academy of Engineering under the Chair in Emerging Technologies Scheme (no. CIET1819_24). R.L.Z.H. acknowledges support from the Royal Academy of Engineering under the Research Fellowship scheme (no. RF\201718\1701), the Isaac Newton Trust (Minute 19.07(d)), Downing College Cambridge through the Kim and Juliana Silverman Research Fellowship, and an EPSRC grant (no. EP/V014498/2). I.B. and B.M. acknowledge support from the Winton Programme for the Physics of Sustainability. B.M. also acknowledges support from a UKRI Future Leaders Fellowship (no. MR/V023926/1) and from the Gianna Angelopoulos Programme for Science, Innovation and Technology. The calculations are conducted using resources provided by the Cambridge Tier-2 system, operated by the University of Cambridge Research Computing Service (www.hpc.cam.ac.uk) and funded by EPSRC Tier-2 capital grant (no. EP/P020259/1).AbstractDetecting low dose rates of X-rays is critical for making safer radiology instruments, but is limited by the absorber materials available. Here, we develop bismuth oxyiodide (BiOI) single crystals into effective X-ray detectors. BiOI features complex lattice dynamics, owing to the ionic character of the lattice and weak van der Waals interactions between layers. Through use of ultrafast spectroscopy, first-principles computations and detailed optical and structural characterisation, we show that photoexcited charge-carriers in BiOI couple to intralayer breathing phonon modes, forming large polarons, thus enabling longer drift lengths for the photoexcited carriers than would be expected if self-trapping occurred. This, combined with the low and stable dark currents and high linear X-ray attenuation coefficients, leads to strong detector performance. High sensitivities reaching 1.1  × 103 μC Gyair−1 cm−2 are achieved, and the lowest dose rate directly measured by the detectors was 22 nGyair s−1. The photophysical principles discussed herein offer new design avenues for novel materials with heavy elements and low-dimensional electronic structures for (opto)electronic applications.</jats:p