Exploring Wave Energy Potential in the UK Using a Whole Systems Modelling Approach

This is the author accepted manuscript. The final version is available from EWTEC via the link in this record.The key market drivers for marine energy are to reduce carbon emissions, and improve security and sustainability of supply. There are other technologies that also meet these requirements, and therefore the marine energy market is dependent on the technology being cost effective, and competitive. The potential UK wave energy market is assessed using ETI’s Energy Systems Modelling Environment (ESME) which uses a multi-vector approach including energy generation, demand, heat, transport, and infrastructure. This will be used to identify scenarios where wave energy forms part of the least-cost energy system for the UK by 2050, and will assess what LCOE reductions are required to improve the commercialisation rate.The author gratefully acknowledges funding support from ETI and the EPSRC RCUK Energy program for the Industrial Doctoral Centre for Offshore Renewable Energy (IDCORE)

Large mesospheric ice particles at exceptionally high altitudes

We here report on the characteristics of exceptionally high Noctilucent clouds (NLC) that were detected with rocket photometers during the ECOMA/MASS campaign at Andøya, Norway 2007. The results from three separate flights are shown and discussed in connection to lidar measurements. Both the lidar measurements and the large difference between various rocket passages through the NLC show that the cloud layer was inhomogeneous on large scales. Two passages showed a particularly high, bright and vertically extended cloud, reaching to approximately 88 km. Long time series of lidar measurements show that NLC this high are very rare, only one NLC measurement out of thousand reaches above 87 km. The NLC is found to consist of three distinct layers. All three were bright enough to allow for particle size retrieval by phase function analysis, even though the lowest layer proved too horizontally inhomogeneous to obtain a trustworthy result. Large particles, corresponding to an effective radius of 50 nm, were observed both in the middle and top of the NLC. The present cloud does not comply with the conventional picture that NLC ice particles nucleate near the temperature minimum and grow to larger sizes as they sediment to lower altitudes. Strong up-welling, likely caused by gravity wave activity, is required to explain its characteristics

Cytochrome P4501A is Induced in Endothelial Cell Lines From the Kidney and Lung of the Bottlenose Dolphin, \u3ci\u3eTursiops truncatus\u3c/i\u3e

Marine mammals respond to the presence of polycyclic and planar halogenated aromatic hydrocarbons (PAH or PHAH) with the induced expression in endothelium of cytochrome P4501A1, regulated through the aryl hydrocarbon receptor (AHR) transcription factor. Physiological responses in other animals, such as edema and inflammation indicate that the endothelium may be compromised by exposure to AHR agonists, which are ubiquitous in the marine environment. In other mammals and fish the cellular and molecular consequences of exposure to AHR agonists have been elucidated in cultured endothelial cells. We have cultured and characterized cetacean endothelial cells (EC) and used them in induction studies. Endothelial cells were cultured from the lung and kidney of the bottlenose dolphin, Tursiops truncates, and exposed to the AHR agonists β-naphthoflavone (βNF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). βNF (1–3 μM) induced significant increases in CYP1A1 (O-deethylation of 7-ethoxyresorufin to resorufin; EROD) activity to 3.6 and 0.92 pmol/mg/min in lung and kidney EC, respectively. TCDD was more potent than βNF, and more efficacious, with maximum induction of CYP1A1 activity of 10.1 and 15.2 pmol/mg/min in lung and kidney EC at 3–10 nM TCDD. The differential response indicates that the lung and kidney endothelial cells in culture retain the ability to respond in a selective manner to specific stimuli. Both the molecular mechanisms of induction and the physiological consequences, especially in the vasculature, of toxicant exposure can be studied in this system

The PTI-suppressing Avr2 effector from Fusarium oxysporum suppresses mono-ubiquitination and plasma membrane dissociation of BIK1

Plant pathogens use effector proteins to target host processes involved in pathogen perception, immune signalling, or defence outputs. Unlike foliar pathogens, it is poorly understood how root-invading pathogens suppress immunity. The Avr2 effector from the tomato root- and xylem-colonizing pathogen Fusarium oxysporum suppresses immune signalling induced by various pathogen-associated molecular patterns (PAMPs). It is unknown how Avr2 targets the immune system. Transgenic AVR2 Arabidopsis thaliana phenocopies mutants in which the pattern recognition receptor (PRR) co-receptor BRI1-ASSOCIATED RECEPTOR KINASE (BAK1) or its downstream signalling kinase BOTRYTIS-INDUCED KINASE 1 (BIK1) are knocked out. We therefore tested whether these kinases are Avr2 targets. Flg22-induced complex formation of the PRR FLAGELLIN SENSITIVE 2 and BAK1 occurred in the presence and absence of Avr2, indicating that Avr2 does not affect BAK1 function or PRR complex formation. Bimolecular fluorescence complementation assays showed that Avr2 and BIK1 co-localize in planta. Although Avr2 did not affect flg22-induced BIK1 phosphorylation, mono-ubiquitination was compromised. Furthermore, Avr2 affected BIK1 abundance and shifted its localization from nucleocytoplasmic to the cell periphery/plasma membrane. Together, these data imply that Avr2 may retain BIK1 at the plasma membrane, thereby suppressing its ability to activate immune signalling. Because mono-ubiquitination of BIK1 is required for its internalization, interference with this process by Avr2 could provide a mechanistic explanation for the compromised BIK1 mobility upon flg22 treatment. The identification of BIK1 as an effector target of a root-invading vascular pathogen identifies this kinase as a conserved signalling component for both root and shoot immunity

Implications of a long-lived basal magma ocean in generating Earth’s ancient magnetic field

Observations of Earth’s magnetic field extending back to 3.45 billion years ago indicate that generation by a core dynamo must be sustained over most of Earth’s history. However, recent estimates of thermal and electrical conductivity of liquid iron at core conditions from mineral physics experiments indicate that adiabatic heat flux is approximately 15 TW, nearly three times larger than previously thought, exacerbating difficulties for driving a core dynamo throughout Earth history by convective core cooling alone. Here, we explore the geomagnetic consequences of a basal magma ocean layer in the lowermost mantle, hypothesized to exist in the early Earth and perhaps surviving until well after the Archean. While the modern, solid lower mantle is an electromagnetic insulator, electrical conductivities of silicate melts are known to be higher, though as yet they are unconstrained for lowermost mantle conditions. We consider a range of possible electrical conductivities and find that for the highest electrical conductivities considered, a long-lived basal magma ocean could be a primary dynamo source region. This would suggest the proposed three magnetic eras observed in paleomagnetic data originate from distinct sources for dynamo generation: from 4.5 to 2.45 Ga within a basal magma ocean, from 2.25 to 0.4 Ga within a superadiabatically cooled liquid core, and from 0.4 Ga to present within a quasi-adiabatic core that includes a solidifying inner core.Keywords: Magma Ocean, Thermal evolution of Earth, Paleomagnetis

Identification of a Chemical That Inhibits the Mycobacterial UvrABC Complex in Nucleotide Excision Repair†

ABSTRACT: Bacterial DNA can be damaged by reactive nitrogen and oxygen intermediates (RNI and ROI) generated by host immunity, as well as by antibiotics that trigger bacterial production of ROI. Thus a pathogen’s ability to repair its DNA may be important for persistent infection. A prominent role for nucleotide excision repair (NER) in disease caused by Mycobacterium tuberculosis (Mtb) was suggested by attenuation of uvrB-deficient Mtb in mice. However, it was unknown if Mtb’s Uvr proteins could execute NER. Here we report that recombinant UvrA, UvrB, and UvrC from Mtb collectively bound and cleaved plasmid DNA exposed to ultraviolet (UV) irradiation or peroxynitrite. We used the DNA incision assay to test the mechanism of action of compounds identified in a high-throughput screen for their ability to delay recovery of M. smegmatis from UV irradiation. 2-(5-Amino-1,3,4-thiadiazol-2-ylbenzo[f]chromen-3-one) (ATBC) but not several closely related compounds inhibited cleavage of damaged DNA byUvrA, UvrB, and UvrC without intercalating in DNA and impaired recovery ofM. smegmatis fromUV irradiation. ATBC di

Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific

Hippocampal volume and declarative memory function in combat-related PTSD

The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed. (JINS, 2009, 15, 830-839.

Post-Myocardial Infarction Cardiogenic Shock Is a Systemic Illness in Need of Systemic Treatment Is Therapeutic Hypothermia One Possibility?

Early observations of cardiogenic shock as a systemic clinical syndrome were first described in 1942. Today, cardiogenic shock remains the leading cause of death among patients hospitalized for myocardial infarction (MI). Mortality rates in post-MI cardiogenic shock approach 50% despite rapid revascularization, optimal medical care, and use of mechanical support. New therapeutic strategies with global systemic effects may offer advances in treatment and outcome in post-MI cardiogenic shock. Therapeutic hypothermia for post-MI cardiogenic shock has multiple potentially beneficial physiologic effects, including the potential to improve post-ischemic cardiac function and hemodynamics, decrease myocardial damage, and reduce end-organ injury from prolonged hypoperfusion. Available data in animal models of post-MI cardiogenic shock and ischemia/reperfusion injury and small case series of human patients with cardiogenic shock suggest its promise as a potential therapeutic strategy for cardiogenic shock in the post-MI setting. We hypothesize that systemic therapeutic hypothermia could decrease morbidity and mortality in post-MI patients with cardiogenic shock and warrants study a new treatment that could be widely available at hospitals worldwide

A Variant PfCRT Isoform Can Contribute to Plasmodium falciparum Resistance to the First-Line Partner Drug Piperaquine

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisininbased combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nucleasebased gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90) or 50% parasite killing (50% lethal dose [LD50]). This mutation also reversed Dd2-mediated CQ resistance, sensitized parasites to amodiaquine, quinine, and artemisinin, and conferred amantadine and blasticidin resistance. Using heme fractionation assays, we demonstrate that PPQ causes a buildup of reactive free heme and inhibits the formation of chemically inert hemozoin crystals. Our data evoke inhibition of heme detoxification in the parasite’s acidic digestive vacuole as the primary mode of both the bisaminoquinoline PPQ and the related 4-aminoquinoline CQ. Both drugs also inhibit hemoglobin proteolysis at elevated concentrations, suggesting an additional mode of action. Isogenic lines differing in their pfmdr1 copy number showed equivalent PPQ susceptibilities. We propose that mutations in PfCRT could contribute to a multifactorial basis of PPQ resistance in field isolates