119 research outputs found
Heterologous Boost Following Mycobacterium bovis BCG Reduces the Late Persistent, Rather Than the Early Stage of Intranasal Tuberculosis Challenge Infection
Adults are the leading population affected by tuberculosis (TB) epidemic and death. Developing an effective vaccine against adult TB is urgently needed. Mycobacterium bovis Bacillus Calmette-Guerin (BCG) prime-heterologous boost strategy has been explored extensively to protect adults against primary TB infection, but the majority of experimental regimens have not improved the protection primed by the BCG vaccine. The reason attributed to the failure remains unknown. In this study, CTT3H-based vaccines, namely DMT adjuvanted CTT3H subunit or DNA vaccine (pCTT3H-DMT), and recombinant adenovirus rAdCTT3H were constructed. Protective efficacy and immunogenicity of BCG prime-CTT3H based boosters were compared in C57BL/c mice models of primary or late persistent TB infection. Similar protective efficacy against early intranasal infection was provided by different CTT3H-based vaccines alone in vaccinated mice, and their protection was inferior to that of the BCG vaccine. In addition, CTT3H-based heterologous boosters did not enhance the protection conferred by the BCG vaccine against primary infection. However, all of these three boosters provided stronger protection against late persistent TB infection than BCG alone, regardless of vaccine types. Although BCG prime-boosters elicited Th1-biased responses to the antigen CTT3H, the number of CTT3H-sepcific IFN-γ-expressing TEM (CD62LloCD44hi) and IL-2-expressing TCM (CD62LhiCD44hi) cells in the spleen was not improved before exposure to Mycobacterium tuberculosis infection. In contrast, IFN-γ+ TEM and IL-2+ TCM cells in spleens, especially in lungs were significantly increased in BCG prime-boosters after exposure vaccination. Our results indicate that BCG prime-boost strategy might be a promising measure for the prevention against late persistent TB infection by induction of IFN-γ+ TEM and IL-2+ TCM cells in the lung, which can be used as alternative biomarkers for guiding the clinical practice and future development of TB vaccine for adults
Long decay length of magnon-polarons in BiFeO3/La0.67Sr0.33MnO3 heterostructures
Long-distance magnon transport is highly desired for magnonics. Here, the authors demonstrate a millimetre-long magnon decay length in multiferroic heterostructures, which is attributed to magnon-polarons induced by the magnetoelastic coupling.
Magnons can transfer information in metals and insulators without Joule heating, and therefore are promising for low-power computation. The on-chip magnonics however suffers from high losses due to limited magnon decay length. In metallic thin films, it is typically on the tens of micrometre length scale. Here, we demonstrate an ultra-long magnon decay length of up to one millimetre in multiferroic/ferromagnetic BiFeO3(BFO)/La0.67Sr0.33MnO3(LSMO) heterostructures at room temperature. This decay length is attributed to a magnon-phonon hybridization and is more than two orders of magnitude longer than that of bare metallic LSMO. The long-distance modes have high group velocities of 2.5 km s(-1) as detected by time-resolved Brillouin light scattering. Numerical simulations suggest that magnetoelastic coupling via the BFO/LSMO interface hybridizes phonons in BFO with magnons in LSMO to form magnon-polarons. Our results provide a solution to the long-standing issue on magnon decay lengths in metallic magnets and advance the bourgeoning field of hybrid magnonics
Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma
Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using “epithelium-macrophage-leukocyte” (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC
Neutrino Physics with JUNO
The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe
Real-time Monitoring for the Next Core-Collapse Supernova in JUNO
Core-collapse supernova (CCSN) is one of the most energetic astrophysical
events in the Universe. The early and prompt detection of neutrinos before
(pre-SN) and during the SN burst is a unique opportunity to realize the
multi-messenger observation of the CCSN events. In this work, we describe the
monitoring concept and present the sensitivity of the system to the pre-SN and
SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is
a 20 kton liquid scintillator detector under construction in South China. The
real-time monitoring system is designed with both the prompt monitors on the
electronic board and online monitors at the data acquisition stage, in order to
ensure both the alert speed and alert coverage of progenitor stars. By assuming
a false alert rate of 1 per year, this monitoring system can be sensitive to
the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos
up to about 370 (360) kpc for a progenitor mass of 30 for the case
of normal (inverted) mass ordering. The pointing ability of the CCSN is
evaluated by using the accumulated event anisotropy of the inverse beta decay
interactions from pre-SN or SN neutrinos, which, along with the early alert,
can play important roles for the followup multi-messenger observations of the
next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure
Potential of Core-Collapse Supernova Neutrino Detection at JUNO
JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve
Detection of the Diffuse Supernova Neutrino Background with JUNO
As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
Facile fabrication of varisized calcium carbonate microspheres as vaccine adjuvants
Functional calcium carbonate (CaCO3) particles of micron and submicron sizes used in catalysis and biomedicine have attracted considerable attention for decades. In this paper, the process parameters for CaCO3 crystallization were systematically investigated. Our experimental results demonstrated the significance of temperature during fabrication. Under the optimized conditions, various uniform-sized and spherical CaCO3 microparticles (MPs) with average diameters from 0.8 mm to 5 mm were facilely and rapidly fabricated via different mixing strategies including mechanical stirring, homogenization, and ultrasonication. The physicochemical characteristics of the CaCO3 microspheres were evaluated. And, the hepatitis B surface antigen (HBsAg) used as a model antigen was encapsulated into the particles (1 mm and 4 mm) for investigating the immune responses elicited after vaccination. In vitro, dendritic cells (DCs) were significantly activated by the MP-based vaccine formulations with up-regulated co-stimulatory molecules expression of CD40 and CD83. After immunization, CaCO3 MPs loaded with HBsAg induced greater lymphocyte activation, more cytokine secretion, higher antigen-specific IgG titers and more memory T cell generation to protect against reinfection. Therefore, the CaCO3 MPs, especially the 1 mm particles, could induce strong cellular and humoral immune responses, probably because of easier uptake and more efficient antigen-presentation by DCs. With the advantages of good biocompatibility, high loading capacity and easy preparation, they could be potentially useful as vaccine adjuvants. These results might provide further design principles for potent inorganic particulate adjuvant and delivery systems.</p
Design of pH-responsive poly(D, L-lactic-co-glycolic acid) nanoparticles to promote immune response
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