Advances in Spectral Techniques for Detection of Pathogenic Microorganisms

The highly contagious viral illness Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus-2, has led to nearly 5 million deaths worldwide. The detection of highly infectious pathogens or novel pathogens causing emerging infectious diseases is highly challenging. Encouragingly, spectral detection—including laser-induced fluorescence spectroscopy, infrared absorption spectroscopy, Raman spectroscopy and their combinations—has been broadly used to detect pathogenic microorganisms on the basis of their physical and chemical characteristics. Surface-enhanced Raman spectroscopy with labels can detect organisms at a minimum concentration of 3 cells/mL. The changes in cells’ biochemical reactions before and after polioviral infection can be detected by Fourier transform infrared spectroscopy. However, the sensitivity and specificity of different spectral detection categories differs, owing to their different detection principles. Flexible detection methods require interdisciplinary researchers familiar with both pathogen biology and instruments. This review summarizes the advances in spectral techniques used in detecting pathogenic microorganism

Integrated bioprocess for conversion of gaseous substrates to liquids

In the quest for inexpensive feedstocks for the cost-effective production of liquid fuels, we have examined gaseous substrates that could be made available at low cost and sufficiently large scale for industrial fuel production. Here we introduce a new bioconversion scheme that effectively converts syngas, generated from gasification of coal, natural gas, or biomass, into lipids that can be used for biodiesel production. We present an integrated conversion method comprising a two-stage system. In the first stage, an anaerobic bioreactor converts mixtures of gases of CO₂ and CO or H₂ to acetic acid, using the anaerobic acetogen Moorella thermoacetica. The acetic acid product is fed as a substrate to a second bioreactor, where it is converted aerobically into lipids by an engineered oleaginous yeast, Yarrowia lipolytica. We first describe the process carried out in each reactor and then present an integrated system that produces microbial oil, using synthesis gas as input. The integrated continuous bench-scale reactor system produced 18 g/L of C16-C18 triacylglycerides directly from synthesis gas, with an overall productivity of 0.19 g⋅L⁻¹⋅h⁻¹ and a lipid content of 36%. Although suboptimal relative to the performance of the individual reactor components, the presented integrated system demonstrates the feasibility of substantial net fixation of carbon dioxide and conversion of gaseous feedstocks to lipids for biodiesel production. The system can be further optimized to approach the performance of its individual units so that it can be used for the economical conversion of waste gases from steel mills to valuable liquid fuels for transportation.United States. Advanced Research Projects Agency-Energy (DE-AR0000059)United States. Department of Energy (DE-SC0008744

Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice

Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.National Major Science and Technology Projects (China) (2012ZX10003-008-006)National Natural Science Foundation (China) (31470895)National Natural Science Foundation (China) (81072499)China. Ministry of Education (Doctoral Fund 20120211110038

Toxoplasma gondii gra5 deletion mutant protects hosts against Toxoplasma gondii infection and breast tumors

Toxoplasma gondii is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. Breast cancer has become a major public health problem and the therapeutic method needs to be further explored. Many similarities exist between the immune responses caused by T. gondii infection and the immunotherapy for cancers. T. gondii dense granule organelles secrete immunogenic dense granule proteins (GRAs). GRA5 is localized to the parasitophorous vacuole membrane in the tachyzoite stage and the cyst wall in the bradyzoite stage. We found that T. gondii ME49 gra5 knockout strain (ME49Δgra5) was avirulent and failed to form cysts but stimulated antibodies, inflammatory cytokines, and leukocytes infiltration in mice. We next investigated the protective efficacy of ME49Δgra5 vaccination against T. gondii infection and tumor development. All the immunized mice survived the challenge infection of either wild-type RH, ME49, VEG tachyzoites, or ME49 cysts. Moreover, ME49Δgra5 tachyzoite inoculation in situ attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1’s lung metastasis. ME49Δgra5 inoculation upregulated the levels of Th1 cytokines and tumor-infiltrating T cells in the tumor microenvironment and triggered anti-tumor responses by increasing the number of natural killer, B, and T cells, macrophages, and dendritic cells in the spleen. Collectively, these results suggested that ME49Δgra5 was a potent live attenuated vaccine against T. gondii infection and breast cancer

Denial of service mitigation approach for IPv6-enabled smart object networks

Denial of service (DoS) attacks can be defined as any third-party action aiming to reduce or eliminate a network's capability to perform its expected functions. Although there are several standard techniques in traditional computing that mitigate the impact of some of the most common DoS attacks, this still remains a very important open problem to the network security community. DoS attacks are even more troublesome in smart object networks because of two main reasons. First, these devices cannot support the computational overhead required to implement many of the typical counterattack strategies. Second, low traffic rates are enough to drain sensors' battery energy making the network inoperable in short times. To realize the Internet of Things vision, it is necessary to integrate the smart objects into the Internet. This integration is considered an exceptional opportunity for Internet growth but, also, a security threat, because more attacks, including DoS, can be conducted. For these reasons, the prevention of DoS attacks is considered a hot topic in the wireless sensor networks scientific community. In this paper, an approach based on 6LowPAN neighbor discovery protocol is proposed to mitigate DoS attacks initiated from the Internet, without adding additional overhead on the 6LoWPAN sensor devices.This work has been partially supported by the Instituto de Telecomunicacoes, Next Generation Networks and Applications Group (NetGNA), Portugal, and by National Funding from the FCT - Fundacao para a Ciencia e Tecnologia through the Pest-OE/EEI/LA0008/2011.Oliveira, LML.; Rodrigues, JJPC.; De Sousa, AF.; Lloret, J. (2013). Denial of service mitigation approach for IPv6-enabled smart object networks. Concurrency and Computation: Practice and Experience. 25(1):129-142. doi:10.1002/cpe.2850S129142251Gershenfeld, N., Krikorian, R., & Cohen, D. (2004). The Internet of Things. Scientific American, 291(4), 76-81. doi:10.1038/scientificamerican1004-76Akyildiz, I. F., Su, W., Sankarasubramaniam, Y., & Cayirci, E. (2002). Wireless sensor networks: a survey. Computer Networks, 38(4), 393-422. doi:10.1016/s1389-1286(01)00302-4Karl, H., & Willig, A. (2005). Protocols and Architectures for Wireless Sensor Networks. doi:10.1002/0470095121IEEE Std 802.15.4-2006 Part 15.4: wireless medium access control (MAC) and physical layer (PHY) specificationsfor low-rate wireless personal area networks (LR-WPANs) 2006ZigBee Alliance ZigBee Specification 2007WirelessHARThomepage 2012 http://www.hartcomm.org/Hui, J. W., & Culler, D. E. (2008). Extending IP to Low-Power, Wireless Personal Area Networks. IEEE Internet Computing, 12(4), 37-45. doi:10.1109/mic.2008.79Kushalnagar N Montenegro G Schumacher C IPv6 over Low-Power Wireless Personal Area Networks (6LoWPANs): Overview, Assumptions, Problem Statement, and Goals 2007Montenegro G Kushalnagar N Hui J Culler D Transmission of IPv6 Packets over IEEE 802.15.4 Networks 2007Shelby Z Thubert P Hui J Chakrabarti S Bormann C Nordmark E 6LoWPAN Neighbor Discovery 2011Zhou, L., Chao, H.-C., & Vasilakos, A. V. (2011). Joint Forensics-Scheduling Strategy for Delay-Sensitive Multimedia Applications over Heterogeneous Networks. IEEE Journal on Selected Areas in Communications, 29(7), 1358-1367. doi:10.1109/jsac.2011.110803Roman, R., & Lopez, J. (2009). Integrating wireless sensor networks and the internet: a security analysis. Internet Research, 19(2), 246-259. doi:10.1108/10662240910952373Wang, Y., Attebury, G., & Ramamurthy, B. (2006). A survey of security issues in wireless sensor networks. 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Energy-efficient and high-accuracy secure data aggregation in wireless sensor networks. Computer Communications, 34(4), 591-597. doi:10.1016/j.comcom.2010.02.026Oliveira, L. M. L., de Sousa, A. F., & Rodrigues, J. J. P. C. (2011). Routing and mobility approaches in IPv6 over LoWPAN mesh networks. International Journal of Communication Systems, 24(11), 1445-1466. doi:10.1002/dac.1228Narten T Nordmark E Simpson W Soliman H Neighbor Discovery for IP version 6 (IPv6) 2007Singh H Beebee W Nordmark E IPv6 Subnet Model: The Relationship between Links and Subnet Prefixes 2010Roman, R., Lopez, J., & Gritzalis, S. (2008). Situation awareness mechanisms for wireless sensor networks. IEEE Communications Magazine, 46(4), 102-107. doi:10.1109/mcom.2008.4481348Sakarindr, P., & Ansari, N. (2007). Security services in group communications over wireless infrastructure, mobile ad hoc, and wireless sensor networks. 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Critical roles of edge turbulent transport in the formation of high-field-side high-density front and density limit disruption in J-TEXT tokamak

This article presents an in-depth study of the sequence of events leading to density limit disruption in J-TEXT tokamak plasmas, with an emphasis on boudary turbulent transport and the high-field-side high-density (HFSHD) front. These phenomena were extensively investigated by using Langmuir probe and Polarimeter-interferometer diagnostics

A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cells

Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers

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$M_{\odot}$ 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