Measurement of turbulent flame speed of natural gas/air mixtures at elevated pressure

Turbulent flame speeds were measured over a range of pressures to 0.8 MPa using a jet flow apparatus fired with a synthetic mixture representing a mid-European natural gas. The equivalence ratio empty set was 0.9. The gas contained significant proportions of ballast gases and higher hydrocarbons. The method adopted was the 'flame angle' technique, using schlieren imaging to obtain the flame vertex angle from the peak density gradient. Image analysis techniques were developed to reduce interpretation errors and give an unbiased result. The data show higher flame speeds than those obtained with pure methane at elevated pressures, using similar methodology, and has an application in numerical modelling of combustors

Gene amplifications associated with the development of hormone- resistant prostate cancer

Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential. Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor. Archival microdissected tumor DNA was extracted, amplified, labeled, and hybridized to Amplione I DNA microarrays containing 57 oncogenes. Results: Genetic instability increased during progression from hormone-sensitive to hormone-resistant cancer (P = 0.008). Amplification frequencies of 15 genes (TERC, MYBL3, HRAS, PI3KCA, JUNB, LAMC2, RAF1, MYC, GARP, SAS, FGFR1, PGY1, MYCL1, MYB, FGR) increased by greater than 10% during hormone escape. Receptor tyrosine kinases were amplified in 73% of cases; this was unrelated to development of hormone resistance. However, downstream receptor tyrosine kinase signaling pathways showed increased amplification rates in resistant tumors for the mitogen-activated protein kinase (FGR/Src-2, HRAS, and RAF1; P = 0.005) and phosphatidylinositol 3'-kinase pathways (FGR/ Src-2, PI3K, and Akt; P = 0.046). Transcription factors regulated by these pathways were also more frequently amplified after escape (MYC family: 21% before versus 63% after, P = 0.027; MYB family: 26 % before versus 53 % after, P = 0.18). Conclusions: Development of clinical hormone escape is linked to phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. These pathways may function independently of the androgen receptor or via androgen receptor activation by phosphorylation, providing novel therapeutic targets

Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia.

This is the peer reviewed version of the article, which has been published in final form at DOI: 10.1113/jphysiol.2014.282889. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Neurons within the CA1 region of the hippocampus are co-activated during high frequency (100-250 Hz) sharp wave ripple (SWR) activity in a manner that likely drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice) which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7-8 month old wild-type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off-line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and points to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia. This article is protected by copyright. All rights reserved.Alzheimer’s Research UKMedical Research Counci

Altered intrinsic pyramidal neuron properties and pathway-specific synaptic dysfunction underlie aberrant hippocampal network function in a mouse model of Tauopathy.

Final published version of article. This article is freely available online through the J Neurosci Author Open Choice option.The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT: Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention.Medical Research Council (MRC)Royal SocietyAlzheimer's Research United Kingdo

Altered synapse stability in the early stages of tauopathy

ArticleThis is the author accepted manuscript. The final version is freely available from Elsevier (Cell Press) via the DOI in this record.Synapse loss is a key feature of dementia but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that, even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly whereas presynaptic boutons are stablised. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically- driven neuronal activity in pre-degenerative stages of the disease.J.D.J. is funded by a BBSRC CASE PhD studentship. Experiments completed in M.C.A.’s laboratory were funded by an MRC centenary award and ARUK Research Fellowship ( ARUK-RF2015-6 ) to J.W., Alzheimer’s Research UK ( ARUK-ESG2014-3 ), the Medical Research Council ( MR/J013188/1 ), and EUFP7 Marie Curie Actions ( PCIG10-GA-2011-303680 ). The authors would like to thank Anna Gawedzka, who helped with the image analysis; Jane Cooper, who assisted with the structural imaging; and the University of Bristol Statistics Helpdesk for advice on mixed-model statistical approaches

A small azhdarchoid pterosaur from the latest Cretaceous, the age of flying giants

Pterosaur fossils from the Campanian–Maastrichtian of North America have been reported from the continental interior, but few have been described from the west coast. The first pterosaur from the Campanian Northumberland Formation (Nanaimo Group) of Hornby Island, British Columbia, is represented here by a humerus, dorsal vertebrae (including three fused notarial vertebrae), and other fragments. The elements have features typical of Azhdarchoidea, an identification consistent with dominance of this group in the latest Cretaceous. The new material is significant for its size and ontogenetic stage: the humerus and vertebrae indicate a wingspan of ca 1.5?m, but histological sections and bone fusions indicate the individual was approaching maturity at time of death. Pterosaurs of this size are exceedingly rare in Upper Cretaceous strata, a phenomenon commonly attributed to smaller pterosaurs becoming extinct in the Late Cretaceous as part of a reduction in pterosaur diversity and disparity. The absence of small juveniles of large species—which must have existed—in the fossil record is evidence of a preservational bias against small pterosaurs in the Late Cretaceous, and caution should be applied to any interpretation of latest Cretaceous pterosaur diversity and success

Risk of SARS-CoV-2 transmission from humans to bats : an Australian assessment

SARS-CoV-2, the cause of COVID-19, infected over 100 million people globally by February 2021. Reverse zoonotic transmission of SARS-CoV-2 from humans to other species has been documented in pet cats and dogs, big cats and gorillas in zoos, and farmed mink. As SARS-CoV-2 is closely related to known bat viruses, assessment of the potential risk of transmission of the virus from humans to bats, and its subsequent impacts on conservation and public health, is warranted. A qualitative risk assessment was conducted by a multi-disciplinary group to assess this risk in bats in the Australian context, with the aim of informing risk management strategies for human activities involving interactions with bats. The overall risk of SARS-CoV-2 establishing in an Australian bat population was assessed to be Low, however with a High level of uncertainty. The outcome of the assessment indicates that, for the Australian situation where the prevalence of COVID-19 in humans is very low, it is reasonable for research and rehabilitation of bats to continue, provided additional biosecurity measures are applied. Risk assessment is challenging for an emerging disease where information is lacking and the situation is changing rapidly; assessments should be revised if human prevalence or other important factors change significantly. The framework developed here, based on established animal disease risk assessment approaches adapted to assess reverse zoonotic transmission, has potential application to a range of wildlife species and situations

Enamel Matrix Derivative Use in Dentistry: An Update

File replaced (incorrect version) on 04/10/2022 by KT (LDS).Following a review of periodontal wound healing, this article discusses techniques designed to optimise periodontal wound healing, including guided-tissue regeneration and periodontal regeneration using enamel matrix derivatives. Enamel matrix derivatives are porcine derived, and are thought to stimulate differentiation, proliferation, migration and mineralization in cells found in periodontal tissues. This article charts the development in surgical techniques to optimise outcomes from regenerative techniques, in addition to explaining complications and how they can be avoided. Recent research relating to use of enamel matrix derivatives as an adjunct to non-surgical periodontal therapy is described, and while the evidence is limited to a single research study, the present article discusses the potential use of this technique in practice, accepting that a cost–benefit analysis would be required for individual patients. CPD/Clinical Relevance: An update for practitioners on developments in use of enamel matrix derivatives in dentistry to allow informed decision-making on the utility and value of using flapless techniques