| 1. |
- Hu, Jinhong, et al.
(författare)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 2. |
- Li, Nannan, et al.
(författare)
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Phytolith and simulation evidence for precipitation-modulated vegetation dynamics along the East Asian monsoon margin
- 2022
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 590
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Tidskriftsartikel (refereegranskat)abstract
- An improved understanding of past interactions between terrestrial vegetation and various forcings, such as climate change, human impact, and paleofire, is crucial for assessing impacts of future global change on terrestrial ecosystems. This study seeks to find the key factor or factors that have driven Holocene vegetation change along the East Asian monsoon margin. Several high-resolution pollen records are reviewed and new phytolith-based paleovegetation reconstructions and physical geochemical datasets are presented from a peatland in northeastern China. Using 108 modern topsoil samples as a training set, canopy cover and vegetation composition are estimated for the period since 5100 cal. yr BP. Variation partitioning analysis (VPA) is used to determine the relative importance of climate change, human impacts, and paleofire disturbance. The generalized dynamic vegetation model LPJ-GUESS is forced with climate anomaly output from an atmospheric general circulation model to simulate vegetation dynamics during the mid-Holocene and the pre-industrial era. The proxy-based estimates are compared to modelling output. Results indicate that regional tree cover varied from 10% to 40% during the past five millennia. The single-core, phytolith-based reconstructions are generally consistent with stacked tree pollen z-scores calculated from different records along the East Asian monsoon margin, implying that mid-Holocene tree cover decrease was persistent and almost synchronous over extensive areas. VPA demonstrates that long-term monsoon marginal vegetation successions were mainly caused by climate effects. Numerical modelling suggests that since the mid-Holocene the retreat of forests along the monsoon margin was primarily associated with precipitation deficits. Our investigation highlights that the precipitation associated with the East Asian monsoon system has exerted a stronger influence than the westerlies on the monsoon margin climate and vegetation change. With ongoing global change, close attention to variations in precipitation patterns and amounts should be especially helpful in efforts aimed at ecological monitoring, change prediction, and restoration.
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| 3. |
- Wang, Dandan, et al.
(författare)
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Ultrafast carrier dynamics of near-band-edge emission in single-crystal ZnO nanorods
- 2011
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Ingår i: Materials research bulletin. - : Elsevier Science B.V., Amsterdam.. - 0025-5408 .- 1873-4227. ; 46:6, s. 937-940
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Tidskriftsartikel (refereegranskat)abstract
- We report on rational synthesis and optical characteristics of highly crystallined ZnO nanorods which were grown by a facile chemical vapor transport method. Temperature-dependent photoluminescence spectra of as-fabricated ZnO nanorods are dominated by near-band-edge emission with a characteristic fine structure due to high crystallinity. Furthermore, the recombination emission involving carrier dynamics of near-band-edge emission in ZnO nanorods was systematically investigated by temperature-dependent time-resolved photoluminescence spectroscopy. Recombination peaks pertaining to the exciton emissions are monitored and resolved in both temporal and spatial regimes.
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| 4. |
- Yu, Miao, et al.
(författare)
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SERS study of single-walled carbon nanotubes on silver films deposited on different substrates
- 2003
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Ingår i: Chemical Journal of Chinese Universities / Gao Deng Xue Xiao Hua Xue Xue Bao. - : Chinese Electronic Periodical Services. - 0251-0790. ; 24:6, s. 1285-1288
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Tidskriftsartikel (refereegranskat)abstract
- Surface-enhanced Raman scattering of single-walled carbon nanotubes (SWNTs) on silver films deposited on various substrates, including sapphire, quartz and glass, has been studied systematically. The characteristic features of G-band and D-band have been analyzed and compared with arc discharged and laser ablation samples. D-band is much more sensitive than G-band. The position and the intensity of the G-band in SERS spectra depend on substrates. The peak shift and absolute intensity of G-band on sapphire is obviously larger than that on glass. The contribution of high frequency vibrations to the D-band is also deendent on substrates. Compared to the SWNTs samples with a high semiconducting tube concentration, the sample with high metallic tube concentration has a stronger interaction with silver films.
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| 5. |
- Zhou, Yin, et al.
(författare)
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Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis
- 2017
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Ingår i: Inflammatory Bowel Diseases. - : LIPPINCOTT WILLIAMS & WILKINS. - 1078-0998 .- 1536-4844. ; 23:1, s. 44-56
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Tidskriftsartikel (refereegranskat)abstract
- Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process. Methods: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-a and interleukin-2 were examined by Luminex. Results: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-a and interleukin-2 were also decreased. Conclusions: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.
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| 6. |
- Ali, Zaheer, et al.
(författare)
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Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris
- 2020
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Ingår i: Developmental Biology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0012-1606 .- 1095-564X. ; 457:2, s. 206-214
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Tidskriftsartikel (refereegranskat)abstract
- The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.
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| 7. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 8. |
- Cheng, M., et al.
(författare)
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Oxidation of Ammonia by Ilmenite under Conditions Relevant to Chemical-Looping Combustion
- 2015
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 1520-5029 .- 0887-0624. ; 29:12, s. 8126-8134
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Tidskriftsartikel (refereegranskat)abstract
- The oxidation of ammonia to NOx and N-2 was investigated under conditions that pertain to the fuel reactor during the chemical-lopping combustion of coal with ilmenite. The catalytic decomposition of NH3, the oxidation of NH3 over ihnenite, and the reduction of NO by reduced ilmenite and NH3 were studied experimentally. The catalytic decomposition of NH3, NO reduction by NH3, and reduced ilmenite were found to be important for N-2 formation. NH3 oxidation over ilmenite was the only way in which NO could be formed in this systerri, with around 18% the NH3 being converted to NO at 850-950 degrees C, The oxidation of NH3 was only slightly influenced by the reactor temperature but was strongly influenced by the concentrations of NH3 and syngas. NO formation was,promoted by high concentrations of NH3 and decreased by high concentrations of syngas. The selectivity of the NH3 toward-NO formation was favored at low concentrations of NH3 and syngas. The conversion of NH3 was complete in most cases, although 15-25% of the NH3 was not converted when the inlet syngas concentration increased to levels higher than 10-30%.
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| 9. |
- Ge, C. R., et al.
(författare)
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Antibodies to Cartilage Oligomeric Matrix Protein Are Pathogenic in Mice and May Be Clinically Relevant in Rheumatoid Arthritis
- 2022
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cartilage oligomeric matrix protein (COMP) is an autoantigen in rheumatoid arthritis (RA) and experimental models of arthritis. This study was undertaken to investigate the structure, function, and relevance of anti-COMP antibodies. Methods We investigated the pathogenicity of monoclonal anti-COMP antibodies in mice using passive transfer experiments, and we explored the interaction of anti-COMP antibodies with cartilage using immunohistochemical staining. The interaction of the monoclonal antibody 15A11 in complex with its specific COMP epitope P6 was determined by x-ray crystallography. An enzyme-linked immunosorbent assay and a surface plasma resonance technique were used to study the modulation of calcium ion binding to 15A11. The clinical relevance and value of serum IgG specific to the COMP P6 epitope and its citrullinated variants were evaluated in a large Swedish cohort of RA patients. Results The murine monoclonal anti-COMP antibody 15A11 induced arthritis in naive mice. The crystal structure of the 15A11-P6 complex explained how the antibody could bind to COMP, which can be modulated by calcium ions. Moreover, serum IgG specific to the COMP P6 peptide and its citrullinated variants was detectable at significantly higher levels in RA patients compared to healthy controls and correlated with a higher disease activity score. Conclusion Our findings provide the structural basis for binding a pathogenic anti-COMP antibody to cartilage. The recognized epitope can be citrullinated, and levels of antibodies to this epitope are elevated in RA patients and correlate with higher disease activity, implicating a pathogenic role of anti-COMP antibodies in a subset of RA patients.
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| 10. |
- He, Yibo, et al.
(författare)
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A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis.
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certainRA synovial fluid proteins such as α-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated α-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA.
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