The Role of Water in the Stability of Cratonic Keels

Cratons are typically underlain by large, deep, and old lithospheric keels (to greater than 200 km depth, greater than 2.5 Ga old) projecting into the asthenosphere (e.g., Jordan, 1978; Richardson et al., 1984). This has mystified Earth scientists as the dynamic and relatively hot asthenosphere should have eroded away these keels over time (e.g., Sleep, 2003; O'Neill et al., 2008; Karato, 2010). Three key factors have been invoked to explain cratonic root survival: 1) Low density makes the cratonic mantle buoyant (e.g., Poudjom Djomani et al., 2001). 2) Low temperatures (e.g., Pollack, 1986; Boyd, 1987), and 3) low water contents (e.g., Pollack, 1986), would make cratonic roots mechanically strong. Here we address the mechanism of the longevity of continental mantle lithosphere by focusing on the water parameter. Although nominally anhydrous , olivine, pyroxene and garnet can accommodate trace amounts of water in the form of H bonded to structural O in mineral defects (e.g., Bell and Rossman, 1992). Olivine softens by orders of magnitude if water (1-1000 ppm H2O) is added to its structure (e.g., Mackwell et al., 1985). Our recent work has placed constraints on the distribution of water measured in peridotite minerals in the cratonic root beneath the Kaapvaal in southern Africa (Peslier et al., 2010). At P greater than 5 GPa, the water contents of pyroxene remain relatively constant while those of olivine systematically decrease from 50 to less than 10 ppm H2O at 6.4 GPa. We hypothesized that at P greater than 6.4 GPa, i.e. at the bottom of the cratonic lithosphere, olivines are essentially dry (greater than 10 ppm H2O). As olivine likely controls the rheology of the mantle, we calculated that the dry olivines could be responsible for a contrast in viscosity between cratonic lithosphere and surrounding asthenosphere large enough to explain the resistance of cratonic root to asthenospheric delamination

Metasomatic Control of Water in Garnet and Pyroxene from Kaapvaal Craton Mantle Xenoliths

Fourier transform infrared spectrometry (FTIR) and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) were used to determine water, rare earth (REE), lithophile (LILE), and high field strength (HFSE) element contents in garnet and pyroxene from mantle xenoliths, Kaapvaal craton, southern Africa. Water enters these nominally anhydrous minerals as protons bonded to structural oxygen in lattice defects. Pyroxene water contents (150-400 ppm in clinopyroxene; 40-250 ppm in orthopyroxene) correlate with their Al, Fe, Ca and Na and are homogeneous within a mineral grains and a xenolith. Garnets from Jagersfontein are chemically zoned for Cr, Ca, Ti and water contents. Garnets contain 0 to 20 ppm H2 Despite the fast diffusion rate of H in mantle m inerals, the observations above indicate that the water contents of mantle xenolith minerals were not disturbed during kimberlite entrainment and that the measured water data represent mantle values. Trace elements in all minerals show various degrees of light REE and LILE enrichments indicative of minimal to strong metasomatism. Water contents of peridotite minerals from the Kaapvaal lithosphere are not related to the degree of depletion of the peridotites. Instead, metasomatism exerts a clear control on the amount of water of mantle minerals. Xenoliths from each location record specific types of metasomatism with different outcomes for the water contents of mantle minerals. At pressures . 5.5 GPa, highly alkaline melts metasomatized Liqhobong and Kimberley peridotites, and increased the water contents of their olivine, pyroxenes and garnet. At higher pressures, the circulation of ultramafic melts reacting with peridotite resulted in co-variation of Ca, Ti and water at the edge of garnets at Jagersfontein, overall decreasing their water content, and lowered the water content of olivines at Finsch Mine. The calculated water content of these melts varies depending on whether the water content of the peridotite (2 wt% HO. 2O) or individual m inerals (<0.5-13 wt% H2O) are used, and also depend on the mineral-melt water partition coefficients. These metasomatic events are thought to have occurred during the Archean and Proterozoic, meaning that the water contents measured here have been preserved since that time and can be used to investigate viscocity and longevity of cratonic mantle roots

Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance

Despite improved outcomes in multiple myeloma (MM), a cure remains elusive. However, even before the current therapeutic era, 5% of patients survived >10 years and we propose that immune factors contribute to this longer survival. We identified patient

Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade

© 2016 Macmillan Publishers Limited. Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-. Normal-for-age telomere lengths indicate that senescence is telomere independent and potentially reversible. p38-mitogen-activated protein kinase, p16 and p21 signalling pathways known to induce senescence were not elevated. Telomerase activity was found to be elevated and this may explain how normal telomere lengths are maintained in senescent cells. T-cell receptor signalling checkpoints were normal but elevated SMAD levels associated with T-cell inactivation were detected and may provide a potential target for the reversal of clonal T-cell dysfunction in MM. Low programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 expression detected on T-cell clones infers that these cells are not exhausted but suggests that there would be a suboptimal response to immune checkpoint blockade in MM. Our data suggest that other immunostimulatory strategies are required in MM

Smelting conditions and smelting products: Experimental insights into the development of iron bloomery furnaces

The material record for bloomery furnaces in Iron Age and Roman Britain is fragmentary and, because of this paucity of evidence, the reconstruction of the ceramic structures used in iron production is difficult. Experiments have nevertheless been carried out to explore the working parameters and efficiency of iron smelting in bowl furnaces (small structures with little structure above ground level, interior measuring about 30 cm in height) (Craddock, 1995; Girbal, 2013) and shaft furnaces (height c.1m) (Smith, 2013; Crew, 2013; Doonan and Dungworth, 2013; Tylecote and Merkel, 1985; Tylecote and Wynne, 1958). These experiments aimed to clarify which furnace is more efficient for iron smelting and therefore what method was most likely used in Iron Age and Roman Britain. It is theorised that iron smelting furnaces developed from bowl structures to shaft structures over time, as smelters sought furnaces which could reach higher temperatures and create more reducing atmospheres (Dungworth 2013; Tylecote and Merkel, 1985; Tylecote and Wynne, 1958). These experiments suggest that the shaft furnace was used as it could meet these requirements. This study looks at the working conditions of a shaft furnace at an intermediary height - between that of a bowl furnace and of a shaft furnace - in order to understand its working parameters and to consequently better understand the progression from a bowl to a 1m high shaft structure

Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies

Multilingual representations for low resource speech recognition and keyword search

© 2015 IEEE. This paper examines the impact of multilingual (ML) acoustic representations on Automatic Speech Recognition (ASR) and keyword search (KWS) for low resource languages in the context of the OpenKWS15 evaluation of the IARPA Babel program. The task is to develop Swahili ASR and KWS systems within two weeks using as little as 3 hours of transcribed data. Multilingual acoustic representations proved to be crucial for building these systems under strict time constraints. The paper discusses several key insights on how these representations are derived and used. First, we present a data sampling strategy that can speed up the training of multilingual representations without appreciable loss in ASR performance. Second, we show that fusion of diverse multilingual representations developed at different LORELEI sites yields substantial ASR and KWS gains. Speaker adaptation and data augmentation of these representations improves both ASR and KWS performance (up to 8.7% relative). Third, incorporating un-transcribed data through semi-supervised learning, improves WER and KWS performance. Finally, we show that these multilingual representations significantly improve ASR and KWS performance (relative 9% for WER and 5% for MTWV) even when forty hours of transcribed audio in the target language is available. Multilingual representations significantly contributed to the LORELEI KWS systems winning the OpenKWS15 evaluation

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Sensory cutaneous papillae in the sea lamprey (Petromyzonmarinus L.) : I. Neuroanatomy and physiology

Molecules present in an animal's environment can indicate the presence of predators,food, or sexual partners and consequently, induce migratory, reproductive, foraging,or escape behaviors. Three sensory systems, the olfactory, gustatory, and solitarychemosensory cell (SCC) systems detect chemical stimuli in vertebrates. While agreat deal of research has focused on the olfactory and gustatory system over theyears, it is only recently that significant attention has been devoted to the SCC sys-tem. The SCCs are microvillous cells that were first discovered on the skin of fish,and later in amphibians, reptiles, and mammals. Lampreys also possess SCCs that areparticularly numerous on cutaneous papillae. However, little is known regarding theirprecise distribution, innervation, and function. Here, we show that sea lampreys(Petromyzon marinus L.) have cutaneous papillae located around the oral disk, nostril,gill pores, and on the dorsal fins and that SCCs are particularly numerous on thesepapillae. Tract-tracing experiments demonstrated that the oral and nasal papillae areinnervated by the trigeminal nerve, the gill pore papillae are innervated by branchialnerves, and the dorsal fin papillae are innervated by spinal nerves. We also character-ized the response profile of gill pore papillae to some chemicals and showed thattrout-derived chemicals, amino acids, and a bile acid produced potent responses.Together with a companion study (Suntres et al., Journal of Comparative Neurology,this issue), our results provide new insights on the function and evolution of the SCCsystem in vertebrates

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others