| 1. |
- Henry, Carole, et al.
(författare)
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Monoclonal Antibody Responses after Recombinant Hemagglutinin Vaccine versus Subunit Inactivated Influenza Virus Vaccine : a Comparative Study
- 2019
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Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 93:21
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells. In order to compare the fine specificity of the antibodies induced by these two novel vaccine platforms, we characterized 42 Flublok-induced monoclonal antibodies (MAbs) and 38 Flucelvax-induced MAbs for avidity, cross-reactivity, and any selectivity toward the head versus the stalk domain. These studies revealed that Flublok induced a greater proportion of MAbs targeting epitopes near the receptor-binding domain on HA head (hemagglutinin inhibition-positive MAbs) than Flucelvax, while the two vaccines induced similar low frequencies of stalk-reactive MAbs. Finally, mice immunized with Flublok and Flucelvax also induced similar frequencies of stalk-reactive antibody-secreting cells, showing that HA head immunodominance is independent of immune memory bias. Collectively, our results suggest that these vaccine formulations are similarly immunogenic but differ in the preferences of the elicited antibodies toward the receptor-binding domain on the HA head.IMPORTANCE: There are ongoing efforts to increase the efficacy of influenza vaccines and to promote production strategies that can rapidly respond to newly emerging viruses. It is important to understand if current alternative seasonal vaccines, such as Flublok and Flucelvax, that use alternate production strategies can induce protective influenza-specific antibodies and to evaluate what type of epitopes are targeted by distinct vaccine formulations.
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| 2. |
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| 3. |
- de Leon, Mony J, et al.
(författare)
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The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.
- 2018
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.
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| 4. |
- Gil-Romera, Graciela, et al.
(författare)
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Long-term fire resilience of the Ericaceous Belt, Bale Mountains, Ethiopia
- 2019
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- Fire is the most frequent disturbance in the Ericaceous Belt (ca 3000-1300 m.a.s.l.), one of the most important plant communities of tropical African mountains. Through resprouting after fire, Erica establishes a positive fire feedback under certain burning regimes. However, present-day human activity in the Bale Mountains of Ethiopia includes fire and grating systems that may have a negative impact on the resilience of the ericaceous ecosystem. Current knowledge of Erica-fire relationships is based on studies of modern vegetation, lacking a longer time perspective that can shed light on baseline conditions for the fire feedback. We hypothesite that fire has influenced Erica communities in the Bale Mountains at millennial time-scales. To test this, we (1) identity the tire history ot the Bale Mountains through a pollen and charcoal record from Garba Guracha, a lake at 3950 m.a.s.l., and (2) describe the long-term bidirectional feedback between wildfire and Erica, which may control the ecosystem's resilience. Our results support fire occurrence in the area since ca 14 000 years ago, with particularly intense burning during the early Holocene, 10.8-6.0 cal ka BP. We show that a positive feedback between Erica abundance and fire occurrence was in operation throughout the Lateglacial and Holocene, and interpret the Ericaceous Bolt of the Ethiopian mountains as a long-term fire resilient ecosystem. We propose that controlled burning should be an integral part of landscape management in the Bale Mountains National Park.
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| 5. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
- Palm, Anna-Karin E., 1983-, et al.
(författare)
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Remembrance of Things Past : Long-Term B Cell Memory After Infection and Vaccination
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
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Forskningsöversikt (refereegranskat)abstract
- The success of vaccines is dependent on the generation and maintenance of immunological memory. The immune system can remember previously encountered pathogens, and memory B and T cells are critical in secondary responses to infection. Studies in mice have helped to understand how different memory B cell populations are generated following antigen exposure and how affinity for the antigen is determinant to B cell fate. Additionally, such studies were fundamental in de fining memory B cell niches and how B cells respond following subsequent exposure with the same antigen. On the other hand, human studies are essential to the development of better, newer vaccines but sometimes limited by the difficulty to access primary and secondary lymphoid organs. However, work using human influenza and HIV virus infection and/or immunization in particular has significantly advanced today's understanding of memory B cells. This review will focus on the generation, function, and longevity of B-cell mediated immunological memory (memory B cells and plasma cells) in response to infection and vaccination both in mice and in humans.
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| 7. |
- Spurdle, Amanda B., et al.
(författare)
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Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
- 2011
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 20:5, s. 1032-1038
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.
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| 8. |
- Thierry-Jebali, N., et al.
(författare)
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Applications of vapor-liquid-solid selective epitaxy of highly p-type doped 4H-SiC: PiN diodes with peripheral protection and improvement of specific contact resistance of ohmic contacts
- 2014
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2013, PTS 1 AND 2. - : Trans Tech Publications. - 9783038350101 ; , s. 639-644
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Konferensbidrag (refereegranskat)abstract
- This work deals with two applications of the Selective Epitaxial Growth of highly p-type doped buried 4H-SiC in Vapor-Liquid-Solid configuration (SEG-VLS). The first application is the improvement of the Specific Contact Resistance (SCR) of contacts made on such p-type material. As a result of the extremely high doping level, SCR values as low as 1.3x10-6 Ω.cm2 have been demonstrated. Additionally, the high Al concentration of the SEG-VLS 4H-SiC material induces a lowering of the Al acceptor ionization energy down to 40 meV. The second application is the fabrication of PiN diodes with SEG-VLS emitter and guard-rings peripheral protection. Influence of some process parameters and crystal orientation on the forward and reverse characteristics of the PiN diodes is discussed. © (2014) Trans Tech Publications, Switzerland.
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| 9. |
- Thierry-Jebali, Nicolas, et al.
(författare)
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Electrical Characterization of PiN Diodes with p(+) layer Selectively Grown by VLS Transport
- 2013
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Ingår i: Silicon Carbide and Related Materials 2012. - : Trans Tech Publications Inc.. ; , s. 911-914
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Konferensbidrag (refereegranskat)abstract
- This paper deals with electrical characterization of PiN diodes fabricated on an 8 degrees off-axis 4H-SiC with a p(++) epitaxial area grown by Vapour-Liquid-Solid (VLS) transport. It provides for the first time evidence that a high quality p-n junction can be achieved by using this technique followed by a High Temperature Annealing (HTA) process.
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| 10. |
- Thierry-Jebali, N., et al.
(författare)
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Very low specific contact resistance measurements made on a highly p-type doped 4H-SiC layer selectively grown by vapor-liquid-solid transport
- 2013
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Ingår i: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 102:21, s. 212108-
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Tidskriftsartikel (refereegranskat)abstract
- This work reports on the performances of ohmic contacts fabricated on highly p-type doped 4H-SiC epitaxial layer selectively grown by vapor-liquid-solid transport. Due to the very high doping level obtained, the contacts have an ohmic behavior even without any annealing process. Upon variation of annealing temperatures, it was shown that both 500 and 800 °C annealing temperature lead to a minimum value of the Specific Contact Resistance (SCR) down to 1.3×10−6 Ω⋅cm2. However, a large variation of the minimum SCR values has been observed (up to 4×10−4 Ω⋅cm2). Possible sources of this fluctuation have been also discussed in this paper.
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