Blocked dihydropteridines as nitric oxide synthase activators

It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings

On the Adjoint Operator in Photoacoustic Tomography

Photoacoustic Tomography (PAT) is an emerging biomedical "imaging from coupled physics" technique, in which the image contrast is due to optical absorption, but the information is carried to the surface of the tissue as ultrasound pulses. Many algorithms and formulae for PAT image reconstruction have been proposed for the case when a complete data set is available. In many practical imaging scenarios, however, it is not possible to obtain the full data, or the data may be sub-sampled for faster data acquisition. In such cases, image reconstruction algorithms that can incorporate prior knowledge to ameliorate the loss of data are required. Hence, recently there has been an increased interest in using variational image reconstruction. A crucial ingredient for the application of these techniques is the adjoint of the PAT forward operator, which is described in this article from physical, theoretical and numerical perspectives. First, a simple mathematical derivation of the adjoint of the PAT forward operator in the continuous framework is presented. Then, an efficient numerical implementation of the adjoint using a k-space time domain wave propagation model is described and illustrated in the context of variational PAT image reconstruction, on both 2D and 3D examples including inhomogeneous sound speed. The principal advantage of this analytical adjoint over an algebraic adjoint (obtained by taking the direct adjoint of the particular numerical forward scheme used) is that it can be implemented using currently available fast wave propagation solvers.Comment: submitted to "Inverse Problems

Not just for the wealthy: Rethinking farmed fish consumption in the Global South

Aquaculture’s contributions to food security in the Global South are widely misunderstood. Dominant narratives suggest that aquaculture contributes mainly to international trade benefiting richer Northern consumers, or provides for wealthy urban consumers in Southern markets. On the supply side, the literature promotes an idealized vision of ‘small-scale’, low input, semi-subsistence farming as the primary means by which aquaculture can contribute to food security, or emphasizes the role of ‘industrial’ export oriented aquaculture in undermining local food security. In fact, farmed fish is produced predominantly by a ‘missing middle’ segment of commercial and increasingly intensive farms, and overwhelmingly remains in Southern domestic markets for consumption by poor and middle income consumers in both urban and rural areas, making an important but underappreciated contribution to global food security

Let them eat carp: Fish farms are helping to fight hunger

First paragraph: Over the past three decades, the global aquaculture industry has risen from obscurity to become a critical source of food for millions of people. In 1990, only 13 percent of world seafood consumption was farmed; by 2014, aquaculture was providing more than half of the fish consumed directly by human beings.  The boom has made farmed fish like shrimp, tilapia and pangasius catfish – imported from countries such as Thailand, China and Vietnam – an increasingly common sight in European and North American supermarkets. As a result, much research on aquaculture has emphasized production for export.  This focus has led scholars to question whether aquaculture contributes to the food security of poorer people in producing countries. Many have concluded it does not. Meanwhile, the industry’s advocates often emphasize the potential for small-scale farms, mainly growing fish for home consumption, to feed the poor. Farms of this kind are sometimes claimed to account for 70 to 80 percent of global aquaculture production

Metagenetic analysis of patterns of distribution and diversity of marine meiobenthic eukaryotes

AimMeiofaunal communities that inhabit the marine benthos offer unique opportunities to simultaneously study the macroecology of numerous phyla that exhibit different life-history strategies. Here, we ask: (1) if the macroecology of meiobenthic communities is explained mainly by dispersal constraints or by environmental conditions; and (2) if levels of meiofaunal diversity surpass existing estimates based on morphological taxonomy. LocationUK and mainland European coast. MethodsNext-generation sequencing techniques (NGS; Roche 454 FLX platform) using 18S nuclear small subunit ribosomal DNA (rDNA) gene. Pyrosequences were analysed using AmpliconNoise followed by chimera removal using Perseus. ResultsRarefaction curves revealed that sampling saturation was only reached at 15% of sites, highlighting that the bulk of meiofaunal diversity is yet to be discovered. Overall, 1353 OTUs were recovered and assigned to 23 different phyla. The majority of sampled sites had c. 60-70 unique operational taxonomic units (OTUs) per site, indicating high levels of beta diversity. The environmental parameters that best explained community structure were seawater temperature, geographical distance and sediment size, but most of the variability (R-2=70%-80%) remains unexplained. Main conclusionsHigh percentages of endemic OTUs suggest that meiobenthic community composition is partly niche-driven, as observed in larger organisms, but also shares macroecological features of microorganisms by showing high levels of cosmopolitanism (albeit on a much smaller scale). Meiobenthic communities exhibited patterns of isolation by distance as well as associations between niche, latitude and temperature, indicating that meiobenthic communities result from a combination of niche assembly and dispersal processes. Conversely, isolation-by-distance patterns were not identified in the featured protists, suggesting that animals and protists adhere to radically different macroecological processes, linked to life-history strategies.Natural Environment Research Council (NERC) [NE/E001505/1, NE/F001266/1, MGF-167]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/27413/2006, SFRH/BPD/80447/2014]; EPSRC [EP/H003851/1]; BBSRC CASE studentship; Unilever; Biotechnology and Biological Sciences Research Council [987347]; Engineering and Physical Sciences Research Council [EP/H003851/1]; Natural Environment Research Council [NE/F001290/1, NE/F001266/1, NE/E001505/1, NBAF010002]info:eu-repo/semantics/publishedVersio

Emerging trends in aquaculture value chain research

This paper introduces a special issue of Aquaculture that brings together the largest collection of research on aquaculture value chains compiled to date, comprising 19 individual papers and this introductory review. The introduction identifies five themes emerging from research on aquaculture value chains in the special issue, namely: multi-polarity, diversity and scale, dynamics of transformation, performance and equity, and technical and institutional innovation. Contrary to much research to date, the papers addressing these themes show how the expansion of aquaculture has resulted highly diverse configurations of production for consumption in the global South. Collectively, the papers highlight the need for greater attention to neglected value chain segments and categories of actor, modes of production, regulation, and innovation, and patterns of access to benefits. The papers synthesized also affirm the need for more rigorous and diverse future value chain research to illuminate the aquaculture sector's ongoing development, and contribute to the sustainable expansion as an increasingly important component of the global food system

A Helmholtz equation solver using unsupervised learning: Application to transcranial ultrasound

Transcranial ultrasound therapy is increasingly used for the non-invasive treatment of brain disorders. However, conventional numerical wave solvers are currently too computationally expensive to be used online during treatments to predict the acoustic field passing through the skull (e.g., to account for subject-specific dose and targeting variations). As a step towards real-time predictions, in the current work, a fast iterative solver for the heterogeneous Helmholtz equation in 2D is developed using a fully-learned optimizer. The lightweight network architecture is based on a modified UNet that includes a learned hidden state. The network is trained using a physics-based loss function and a set of idealized sound speed distributions with fully unsupervised training (no knowledge of the true solution is required). The learned optimizer shows excellent performance on the test set, and is capable of generalization well outside the training examples, including to much larger computational domains, and more complex source and sound speed distributions, for example, those derived from x-ray computed tomography images of the skull.Comment: 23 pages, 13 figure

Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009.

BACKGROUND: In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. OBJECTIVE: To explain recent CHD trends in Tunisia between 1997 and 2009. METHODS: DATA SOURCES: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. ANALYSIS: Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). RESULTS: CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). CONCLUSIONS: Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive