110 research outputs found
High Purcell factor generation of indistinguishable on-chip single photons
On-chip single-photon sources are key components for integrated photonic quantum technologies. Semiconductor quantum dots can exhibit near-ideal single-photon emission, but this can be significantly degraded in on-chip geometries owing to nearby etched surfaces. A long-proposed solution to improve the indistinguishablility is to use the Purcell effect to reduce the radiative lifetime. However, until now only modest Purcell enhancements have been observed. Here we use pulsed resonant excitation to eliminate slow relaxation paths, revealing a highly Purcell-shortened radiative lifetime (22.7 ps) in a waveguide-coupled quantum dot–photonic crystal cavity system. This leads to near-lifetime-limited single-photon emission that retains high indistinguishablility (93.9%) on a timescale in which 20 photons may be emitted. Nearly background-free pulsed resonance fluorescence is achieved under π-pulse excitation, enabling demonstration of an on-chip, on-demand single-photon source with very high potential repetition rates
Aging Alters Functionally Human Dermal Papillary Fibroblasts but Not Reticular Fibroblasts: A New View of Skin Morphogenesis and Aging
Understanding the contribution of the dermis in skin aging is a key question, since this tissue is particularly important for skin integrity, and because its properties can affect the epidermis. Characteristics of matched pairs of dermal papillary and reticular fibroblasts (Fp and Fr) were investigated throughout aging, comparing morphology, secretion of cytokines, MMPs/TIMPs, growth potential, and interaction with epidermal keratinocytes. We observed that Fp populations were characterized by a higher proportion of small cells with low granularity and a higher growth potential than Fr populations. However, these differences became less marked with increasing age of donors. Aging was also associated with changes in the secretion activity of both Fp and Fr. Using a reconstructed skin model, we evidenced that Fp and Fr cells do not possess equivalent capacities to sustain keratinopoiesis. Comparing Fp and Fr from young donors, we noticed that dermal equivalents containing Fp were more potent to promote epidermal morphogenesis than those containing Fr. These data emphasize the complexity of dermal fibroblast biology and document the specific functional properties of Fp and Fr. Our results suggest a new model of skin aging in which marked alterations of Fp may affect the histological characteristics of skin
Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin
Abstract
Background
One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity.
Methods
RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined.
Results
These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines.
Conclusion
The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic
Exclusive J/ψ detection and physics with ECCE
The file available on this institutional repository is an arXiv preprint which may not have been certified by peer review. The definitive version of record published by Elsevier is available at https://doi.org/10.48550/arXiv.2207.10356.Copyright © The Authors 2023. The EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been recommended as a reference design for the proposed Electron-Ion Collider (EIC) program. This paper presents simulation studies of exclusive J/ψ detection and selected physics impact results in EIC using the projected ECCE detector concept. Exclusive quarkonium photoproduction is one of the most popular processes in EIC, which has a large cross section and a simple final state. Due to the gluonic nature of the exchange Pomeron, this process can be related to the gluon distributions in the nucleus. Preliminary results estimate the excellent statistics benefited from the large cross section of J/ψ photoproduction and superior performance of ECCE detector concept. The precise measurement of exclusive J/ψ photoproduction at EIC will help us to more deeply understand nuclear gluon distributions, near threshold production mechanism and nucleon mass structure.X. Li and W. Zha are supported by the National Natural Science Foundation of China (12005220, 12175223) and MOST (2018YFE0104900). The authors would like to thank the ECCE Consortium for performing a full simulation of their detector design, for providing up-to-date information on EIC run conditions, and for suggestions and comments on the manuscript. X. Li and W. Zha would like to thank Y. Zhou for useful suggestions and discussions related to this analysis.
W. Zha is supported by Anhui Provincial Natural Science Foundation No. 2208085J23 and Youth Innovation Promotion Association of Chinese Academy of Sciences.
AANL group are supported by the Science Committee of RA , in the frames of the research project
21AG-1C028
Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds
© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds
CVE: an R package for interactive variant prioritisation in precision oncology
BACKGROUND: An increasing number of precision oncology programmes are being launched world-wide. To support this development, we present the Cancer Variant Explorer (CVE), an R package with an interactive Shiny web browser interface. RESULTS: Leveraging Oncotator and the Drug Gene Interaction Database, CVE offers exploration of variants within single or multiple tumour exomes to identify drivers, resistance mechanisms and to assess druggability. We present example applications including the analysis of an individual patient and a cohort-wide study, and provide a first extension of CVE by adding a tumour-specific co-expression network. CONCLUSIONS: The CVE package allows interactive variant prioritisation to expedite the analysis of cancer sequencing studies. Our framework also includes the prioritisation of druggable targets, allows exploratory analysis of tissue specific networks and is extendable for specific applications by virtue of its modular design. We encourage the use of CVE within translational research studies and molecular tumour boards. The CVE package is available via Bioconductor ( http://bioconductor.org/packages/CVE/).AM was supported by the National Institute for Health Research, Biomedical Research Centre (NIHR Cambridge BRC) and the German National Academic Foundation (Studienstiftung des deutschen Volkes). We would like also to acknowledge the support of The University of Cambridge, Cancer Research UK Cambridge Centre and Hutchison Whampoa Limited. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 337905. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Scientific computing plan for the ECCE detector at the Electron Ion Collider
This is the arXiv pre-print which has not been peer reviewed. It is made available under a Creative Commons (CC BY) Attribution Lciense. The corrected version of record is available at: https://doi.org/10.1016/j.nima.2022.167859.Cite as: arXiv:2205.08607 [physics.ins-det]
(or arXiv:2205.08607v1 [physics.ins-det] for this version)
https://doi.org/10.48550/arXiv.2205.08607
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Journal reference: NIMA 1047, 167859 (2023)
Related DOI:
https://doi.org/10.1016/j.nima.2022.167859
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Submission history
From: Joseph Osborn [view email]
[v1] Tue, 17 May 2022 19:53:56 UTC (29,605 KB)Copyright © 2022 The Author(s). The Electron Ion Collider (EIC) is the next generation of precision QCD facility to be built at Brookhaven National Laboratory in conjunction with Thomas Jefferson National Laboratory. There are a significant number of software and computing challenges that need to be overcome at the EIC. During the EIC detector proposal development period, the ECCE consortium began identifying and addressing these challenges in the process of producing a complete detector proposal based upon detailed detector and physics simulations. In this document, the software and computing efforts to produce this proposal are discussed; furthermore, the computing and software model and resources required for the future of ECCE are described.Office of Nuclear Physics in the Office of Science in the Department of Energy, USA; National Science Foundation, USA; Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD), USA 20200022DR
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