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- Gribenski, Natacha, et al.
(författare)
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Re-evaluation of MIS 3 glaciation using cosmogenic radionuclide and single grain luminescence ages, Kanas Valley, Chinese Altai
- 2018
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 33:1, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- Previous investigations observed a period of major glacial advances in Central Asia during marine oxygen isotope stage (MIS) 3 (57–29 ka), out of phase with global ice volume records. We have re-examined the Kanas moraine complex in the Altai Mountains of Central Asia, where an MIS 3 glaciation had been previously inferred. New and consistent cosmogenic exposure and single-grain luminescence ages indicate that the Kanas complex was formed during MIS 2 (29–12 ka), which brings its timing in line with the global ice volume record. We also identified a lateral moraine from a more extensive ice extent that dates to late MIS 5/MIS 4. To place our results in a wider contextual framework, we review the chronologies of another 26 proposed major MIS 3 glacial advances in Central Asia. For most of these sites, we find that the chronological data do not provide an unequivocal case for MIS 3 glaciation. Copyright © 2017 John Wiley & Sons, Ltd.
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- Stokes, Chris R., et al.
(författare)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Forskningsöversikt (refereegranskat)abstract
- Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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- Tobias, J., et al.
(författare)
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A New Strategy Toward B Cell-Based Cancer Vaccines by Active Immunization With Mimotopes of Immune Checkpoint Inhibitors
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effectsin vivofollowing active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, forin vivoevaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized byin vitroassays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growthin vivowas observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.
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- Guralnik, B., et al.
(författare)
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OSL-thermochronometry using bedrock quartz : A note of caution
- 2015
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Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 25, s. 37-48
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Tidskriftsartikel (refereegranskat)abstract
- Optically stimulated luminescence (OSL) thermochronometry is an emerging application, whose capability to record sub-Million-year thermal histories is of increasing interest to a growing number of subdisciplines of Quaternary research. However, several recent studies have encountered difficulties both in extraction of OSL signals from bedrock quartz, and in their thermochronometric interpretation, thus highlighting the need for a methodological benchmark. Here, we investigate the characteristic OSL signals from quartz samples across all major types of bedrock and covering a wide range of chemical purities. High ratios of infrared to blue stimulated luminescence (IRSL/BLSL), an insensitive 'fast' OSL component, and anomalously short recombination lifetimes seen in time-resolved luminescence (TROSL), are often encountered in quartz from crystalline (magmatic and metamorphic) bedrock, and may hamper successful OSL dating. Furthermore, even when the desirable signal is present, its concentration might be indistinguishable from its environmental steady-state prediction, thus preventing its conversion to a cooling or heating history. We explore the saturation properties and the thermal activation parameters of various OSL signals in quartz to outline the capabilities and limitations for their use in low-temperature thermochronometry.
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