Ice-melt rates during volcanic eruptions within water-drained, low pressure subglacial cavities

Subglacial volcanism generates proximal and distal hazards including large-scale flooding and increased levels of explosivity. Direct observation of subglacial volcanic processes is infeasible; therefore, we model heat transfer mechanisms during subglacial eruptions under conditions where cavities have become depressurized by connection to the atmosphere.We consider basaltic eruptions in a water-drained, low-pressure subglacial cavity, including the case when an eruption jet develops. Such drained cavities may develop on sloping terrain, where ice may be relatively shallow and where gravity drainage of meltwater will be promoted. We quantify, for the first time, the heat fluxes to the ice cavity surface that result from steam condensation during free convection at atmospheric pressure and from direct and indirect radiative heat transfer from an eruption jet. Our calculations indicate that the direct radiative heat flux from a lava fountain (a “dry” end-member eruption jet) to ice is c. 25 kW m-2 and is a minor component. The dominant heat transfer mechanism involves free convection of steam within the cavity; we estimate the resulting condensation heat flux to be c. 250 kW m-2. Absorption of radiation froma lava fountain by steamenhances convection, but the increase in condensing heat flux is modest at c. 25 kW m-2. Overall, heat fluxes to the ice cavity surface are likely to be no greater than c. 300 kW m-2. These are comparable with heat fluxes obtained by single phase convection of water in a subglacial cavity but much less than those obtained by two-phase convection

Ice-melt rates by steam condensation during explosive subglacial eruptions

Subglacial volcanism melts cavities in the overlying ice. These cavities may be flooded with meltwater or they may be fully or partially drained. We quantify, for the first time, heat transfer rates by condensation of steam on the walls and roof of a fully or partially drained subglacial eruption cavity. Our calculations indicate that heat fluxes of up to 1 MW m−2 may be obtained when the bulk vapor in the cavity is in free convection. This is considerably smaller than heat fluxes inferred from ice penetration rates in recent subglacial eruptions. Forcing of the convection by momentum transfer from an eruption jet may allow heat fluxes of up to 2 MW m−2, consistent with values inferred for the Gjálp 1996 subglacial eruption. Vapor-dominated cavities in which vapor-liquid equilibrium is maintained have thermal dynamic responses that are an order of magnitude faster than the equivalent flooded cavities

Experimental insights into pyroclast‐ice heat transfer in water‐drained, low pressure cavities during subglacial explosive eruptions

Subglacial explosive volcanism generates hazards that result from magma-ice interaction, including large flow rate meltwater flooding and fine-grained volcanic ash. We consider eruptions where subglacial cavities produced by ice melt during eruption establish a connection to the atmosphere along the base of the ice sheet that allows accumulated meltwater to drain. The resulting reduction of pressure initiates or enhances explosive phreatomagmatic volcanism within a steam-filled cavity with pyroclast impingement on the cavity roof. Heat transfer rates to melt ice in such a system have not, to our knowledge, been assessed previously. To study this system, we take an experimental approach to gain insight into the heat transfer processes and to quantify ice melt rates. We present the results of a series of analogue laboratory experiments in which a jet of steam, air, and sand at approximately 300°C impinged on the underside of an ice block. A key finding was that as the steam to sand ratio was increased, behavior ranged from predominantly horizontal ice melting to predominantly vertical melting by a mobile slurry of sand and water. For the steam to sand ratio that matches typical steam to pyroclast ratios during subglacial phreatomagmatic eruptions at ~300°C, we observed predominantly vertical melting with upward ice melt rates of 1.5 mm s−1, which we argue is similar to that within the volcanic system. This makes pyroclast-ice heat transfer an important contributing ice melt mechanism under drained, low-pressure conditions that may precede subaerial explosive volcanism on sloping flanks of glaciated volcanoes

Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer

Background: The majority (90%) of anal cancers are human papillomavirus (HPV)-driven, identified using immunochemistry for p16. Compared with HPV? patients, those with HPV+ disease generally show improved survival, although relapse rates around 25% indicate a need for further stratification of this group.Methods: Using two cohorts of anal cancer, previously characterised for p16, we assessed the prognostic value of tumour-infiltrating lymphocytes (TILs).Results: Tumour-infiltrating lymphocyte scores were used to stratify p16+ cases, where tumours with absent/low levels of TIL had a relapse-free rate of 63%, as opposed to 92% with high levels of TIL (log rank P=0.006).Conclusions: Assessment of TIL adds to p16 status in the prognosis of anal cancer following chemo-radiotherapy and provides evidence of the clinical importance of the immune response

The Naturalized Gender Order Of Rock and Roll

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66933/2/10.1177_019685999501900104.pd

Impact on Malaria Parasite Multiplication Rates in Infected Volunteers of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909

BACKGROUND: Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. METHODS: In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. RESULTS: A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]). CONCLUSIONS: Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. TRIAL REGISTRATION: ClinicalTrials.gov [NCT00984763]

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Genome Sequence of the Pea Aphid Acyrthosiphon pisum

Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio