370 research outputs found
Cost performance and risk in the construction of offshore and onshore wind farms
This article investigates the risk of cost overruns and underruns occurring in the construction of 51 onshore and offshore wind farms commissioned between 2000 and 2015 in 13 countries. In total, these projects required about 63 million per windfarm, although 20 projects within the sample (39%) did not exhibit cost overruns. The majority of onshore wind farms exhibit cost underruns while for offshore wind farms the results have a larger spread. Interestingly, no significant relationship exists between the size (in total MWor per individual turbine capacity) of a windfarm and the severity of a cost overrun. Nonetheless, there is an indication that the risk increases for larger wind farms at greater distances offshore using new types of turbines and foundations. Overall, the mean cost escalation for onshore projects is 1.7% and 9.6% for offshore projects, amounts much lower than those for other energy infrastructure
Mesoscopic organization reveals the constraints governing C. elegans nervous system
One of the biggest challenges in biology is to understand how activity at the
cellular level of neurons, as a result of their mutual interactions, leads to
the observed behavior of an organism responding to a variety of environmental
stimuli. Investigating the intermediate or mesoscopic level of organization in
the nervous system is a vital step towards understanding how the integration of
micro-level dynamics results in macro-level functioning. In this paper, we have
considered the somatic nervous system of the nematode Caenorhabditis elegans,
for which the entire neuronal connectivity diagram is known. We focus on the
organization of the system into modules, i.e., neuronal groups having
relatively higher connection density compared to that of the overall network.
We show that this mesoscopic feature cannot be explained exclusively in terms
of considerations, such as optimizing for resource constraints (viz., total
wiring cost) and communication efficiency (i.e., network path length).
Comparison with other complex networks designed for efficient transport (of
signals or resources) implies that neuronal networks form a distinct class.
This suggests that the principal function of the network, viz., processing of
sensory information resulting in appropriate motor response, may be playing a
vital role in determining the connection topology. Using modular spectral
analysis, we make explicit the intimate relation between function and structure
in the nervous system. This is further brought out by identifying functionally
critical neurons purely on the basis of patterns of intra- and inter-modular
connections. Our study reveals how the design of the nervous system reflects
several constraints, including its key functional role as a processor of
information.Comment: Published version, Minor modifications, 16 pages, 9 figure
Physics, Topology, Logic and Computation: A Rosetta Stone
In physics, Feynman diagrams are used to reason about quantum processes. In
the 1980s, it became clear that underlying these diagrams is a powerful analogy
between quantum physics and topology: namely, a linear operator behaves very
much like a "cobordism". Similar diagrams can be used to reason about logic,
where they represent proofs, and computation, where they represent programs.
With the rise of interest in quantum cryptography and quantum computation, it
became clear that there is extensive network of analogies between physics,
topology, logic and computation. In this expository paper, we make some of
these analogies precise using the concept of "closed symmetric monoidal
category". We assume no prior knowledge of category theory, proof theory or
computer science.Comment: 73 pages, 8 encapsulated postscript figure
Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>
Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling
Heterostructures for High Performance Devices
Contains an introduction and reports on ten research projects.Charles S. Draper Laboratory, Contract DL-H-315251Joint Services Electronics Program, Contract DAAL03-89-C-0001National Science Foundation Grant, Grant EET 87-03404MIT FundsInternational Business Machines CorporationNational Science Foundation Grant ECS 84-1317
Green Urbanism and its Application to Singapore
Green urbanism has been applied to cities but not in Asia. Seven characteristics of green urbanism are outlined and then applied to Singapore. The Renewable City is not yet a concept for Singapore. The Carbon Neutral City is being developed for an island Palau Ubin and by some firms but not to significant sectors or parts of urban Singapore. The Distributed City is being developed around Singapore’s polycentric model but needs specific infrastructure plans similar to ones developed by Singapore for Tianjin Eco-City. The Biophillic City is being developed as a world first through its Skyrise Greenery initiative and urban landscaping. The Eco-Efficient City is also being demonstrated through Singapore closing the loop on their water and solid waste systems. The Place Based City is very evident in all its 22 sub centres. And the Sustainable Transport City is an Asian leader in integrated transport planning though there are signs of this becoming harder to achieve
An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor
Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote apoptosis of cancer cells. We performed a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses, and thus identify factors that might predict drug sensitivity in cancers. Because the drug's actions play out over several days, we developed an intermittent imaging screen. Live HeLa cells expressing GFP-tagged histone H2B were imaged at 0, 24 and 48 hours after drug addition, and images were analyzed using open-source software that incorporates machine learning. This screen effectively identified siRNAs that caused increased mitotic arrest at low drug concentrations (enhancers), and vice versa (suppressors), and we report siRNAs that caused both effects. We then classified the effect of siRNAs for 15 genes where 3 or 4 out of 4 siRNA oligos tested were suppressors as assessed by time lapse imaging, and by testing for suppression of mitotic arrest in taxol and nocodazole. This identified 4 phenotypic classes of drug suppressors, which included known and novel genes. Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology
Amyloid-β Inhibits No-cGMP Signaling in a CD36- and CD47-Dependent Manner
Amyloid-β interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-β shares this inhibitory activity. Amyloid-β inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-β. Functional interaction of amyloid-β with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-β were active. In contrast, amyloid-β did not compete with the known ligand SIRPα for binding to CD47. However, both receptors were necessary for amyloid-β to inhibit cGMP accumulation. These data suggest that amyloid-β interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-β can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease
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