2,454 research outputs found
Participatory Experimentation with Energy Law:Digging in a ‘Regulatory Sandbox’ for Local Energy Initiatives in the Netherlands
To facilitate energy transition, regulators have devised ‘regulatory sandboxes’ to create a participatory experimentation environment for exploring revision of energy law in several countries. These sandboxes allow for a two-way regulatory dialogue between an experimenter and an approachable regulator to innovate regulation and enable new socio-technical arrangements. However, these experiments do not take place in a vacuum but need to be formulated and implemented in a multi-actor, polycentric decision-making system through collaboration with the regulator but also energy sector incumbents, such as the distribution system operator. Therefore, we are exploring new roles and power division changes in the energy sector as a result of such a regulatory sandbox. We researched the Dutch executive order ‘experiments decentralized, sustainable electricity production’ (EDSEP) that invites homeowners’ associations and energy cooperatives to propose projects that are prohibited by extant regulation. Local experimenters can, for instance, organise peer-to-peer supply and determine their own tariffs for energy transport in order to localize, democratize, and decentralize energy provision. Theoretically, we rely on Ostrom’s concept of polycentricity to study the dynamics between actors that are involved in and engaging with the participatory experiments. Empirically, we examine four approved EDSEP experiments through interviews and document analysis. Our conclusions focus on the potential and limitations of bottom-up, participatory innovation in a polycentric system. The most important lessons are that a more holistic approach to experimentation, inter-actor alignment, providing more incentives, and expert and financial support would benefit bottom-up participatory innovation
Corrosion and tribocorrosion behavior of Ti-Alumina composites
This work focus on the corrosion and wear properties of titanium reinforced with 1% wt. alumina particles, produced by a combination of colloidal techniques and powder metallurgy. The alumina particles were added to control the grain growth of titanium during sintering, and simultaneously to increase hardness and wear resistance. Colloidal techniques permitted a homogeneous dispersion of alumina particles on the surface of fine Ti particles by the formulation of stable aqueous suspensions that were further processed by spray-dry to obtain spherical granules with improved compressibility. Ti-Alumina samples were produced by uniaxial pressing of granules and vacuum sintering leading to materials with homogeneous microstructure, a reduction of grain size higher than 50 % with respect to pure titanium, and a sensible increase in hardness. But the addition of ceramic particles can also have an influence on the corrosion behavior that is one of the most interesting properties of titanium alloys, and on wear resistance, that is one of the drawbacks of Ti. Moreover, the study of simultaneous action of wear and corrosion (tribocorrosion) is an area of highest interest in applications like biomedical or automotive. The corrosion behavior was evaluated by Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PP) in NaCl at two concentrations (0.9 % and 3.5 %) and temperatures (37 °C, and room temperature). Tribocorrosion tests were performed using a reciprocating ball-on-plate tribometer where a 10 mm diameter alumina ball was used as counter material, and 10 N normal load was applied during 30 min in the same concentrations and temperatures of NaCl as in the static corrosion test s. The results showed a clear improvement of wear resistance on the composite without reducing the corrosion behavior in both conditions.(undefined)info:eu-repo/semantics/publishedVersio
Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences
BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).
RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6 × 10
CONCLUSION: These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits
Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis
Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors.
Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events.
Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness.
Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings
Spectroscopic characterization, antimicrobial activity and molecular docking study of novel azo-imine functionalized sulphamethoxazoles
Financial support from University Grants Commission (F.42-333/2013(SR)) and the Council of Scientific and Industrial Research (01(2894)/09/EMR-II), New Delhi are gratefully acknowledged.[SMX—N=N—C6H3—(p-OH)(m—CHO)] ( 1 ) reacts with ArNH2 to synthesize Schiff bases, [SMX—N=N—C6H3—(pOH)(m—HC=N—Ar)] (Ar =—C6H5 ( 2a ), —C6H4—p—CH3 ( 2b ), —C6H4—p—OCH3 ( 2c ), —C6H4—p—Cl ( 2d ), —C6H4—p—NO2 ( 2e ), —C10H7 ( 2f )) and the products have been assessed for antibacterial properties against Gram positive bacteria, B. subtillis: IC50 (μg/ml): 39.2 ( 1 ), 60.1 ( 2a ), 64.0 ( 2b ), 85.6 ( 2c ), 55.1 ( 2d ), 88.4 ( 2e ) and 65.1 ( 2f ); and Gram negative bacteria, E. coli: IC50 (μg/ml): 159.0 ( 1 ), 151.4 ( 2a ), 155.3 ( 2b ), 140 ( 2c ), 156.0 ( 2d ), 153.5 ( 2e ) and 157 ( 2f ). The cell line toxicity (Vero cells) has also been evaluated with these compounds and EC50 (μg/ml) values are 129.9 ( 1 ), 74.2 ( 2a ) and 93.0 ( 2b ), 191.9 ( 2c ), 99.1 ( 2d ), 93.2 ( 2e ) and 62.0 ( 2f ). The anti-viral efficiency against harpies virus (HSV1F ATCC-733) infection demonstrates that the compound 1 has highest selectivity index (CC50/EC50), 5.06 than the compounds 2a-f (CC50/EC50: 1.18 ( 2a ), 1.42 ( 2b ), 3.50 ( 2c ), 1.45 ( 2d ), 1.58 ( 2e ), 1.29 ( 2f )). The compounds have been spectroscopically characterized and the structural confirmation has been established in one case by single crystal X-ray diffraction studies of 2c . In silico Molecular Docking study has been done using optimized geometries of the compounds to search the most favored binding mode of these drugs and hence useful to explain their competitive drug efficiency.PostprintPeer reviewe
Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences
Background Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718). Results We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6 x 10(-8)), which has previously been associated with numerous hematological parameters; and a burden of rare variants in the TMBIM1 gene (P = 3.0 x 10(-8)), which has been reported to protect against non-alcoholic fatty liver disease. We also found that MT-CN is strongly associated with insulin levels (P = 2.0 x 10(-21)) and other metabolic syndrome (metS)-related traits. Using a Mendelian randomization framework, we show evidence that MT-CN measured in blood is causally related to insulin levels. We then applied an MT-CN polygenic risk score (PRS) derived from Finnish data to the UK Biobank, where the association between the PRS and metS traits was replicated. Adjusting for cell counts largely eliminated these signals, suggesting that MT-CN affects metS via cell-type composition. Conclusion These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits.Peer reviewe
Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India.
Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India.The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/refractory to infection and 3) have had past exposure to sand flies.It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locations, more precise epidemiological models can be produced. The suite of data collected can also be used to inform the national programme if supplementary vector control tools, in addition to IRS, are required to address the issues of people sleeping outside
A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules
Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells. Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues, diffusional barriers, or molecular cross-linking. What prevents positive feedback from amplifying inevitable biological noise when an un-clustered “off” state is desired? And, what limits the spread of clusters when an “on” state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. The emergence of a dominant cluster for finite numbers of molecules is partly a phenomenon of random sampling, analogous to the fixation or loss of neutral mutations in finite populations. We refer to our model as the “neutral drift polarity model.” Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization
GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI
Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies
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