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Tuesday, 10 November , Add to calendar Biophysical characterization of the G-protein alpha subunit from A. Friday, 13 November , Add to calendar Structure and dynamic studies of nuclear receptors: Transcription regulation through phosphorylation. Friday, 22 January , Add to calendar Secretion of an acid phosphatase to acquire host nutrients by the human malaria parasite Ingrid B. Friday, 13 August , Add to calendar Structural studies on enzymes from the lysine biosynthetic pathway from M.
Friday, 20 May , Add to calendar Electron and x-ray tomography and super-resolution optical imaging of the malaria parasite. Friday, 2 December , Add to calendar Bridging the gap between protein structure and light microscopy. Friday, 2 November , Add to calendar Constructing and validating structural models obtained by small-angle X-ray scattering. Monday, 31 March , Add to calendar Computational protein design algorithms allow both the refinement of crystal structures and the design of macromolecules with new functions.
Friday, 17 April , Add to calendar M. Friday, 4 December , Add to calendar Pupylation in M. PEroXisomal protein import to in cellulo crystals. Friday, 2 September , Add to calendar The molecular 'exchange' that decides the fate of commissural axon. Friday, 16 September , Add to calendar Beyond the prokaryotic ribosome: structural and functional insights into eukaryotic and mitochondrial ribosomes Nenad Ban, Inst.
Friday, 21 October , Add to calendar Validating cryo-EM based atomic models using X-ray crystallography tools. Friday, 9 June , Add to calendar Do microbes control the mind? Schneider Seminar Room 48e show abstract hide abstract. Friday, 15 September , Add to calendar Structure and function of a peptide transporter from E.
Friday, 20 October , Add to calendar "What you need to know before you need it: Mandatory guidelines for reporting and depositing small angle scattering data. Tuesday, 19 June , Add to calendar Surprises in the mechanism of action of the antibiotic D-cycloserine.
Friday, 3 August , Add to calendar When genomics meets structural biology: insights into E. Friday, 7 September , Add to calendar The ageing of the human haematopoietic stem cell niche. Cancelled - Friday, 12 October , Add to calendar "Netrin-1 and its receptors - bridging the gap between adhesion and axon guidance". Friday, 21 June , Add to calendar Down syndrome cell adhesion molecule: an adhesion sensor? Friday, 22 January , Add to calendar Does sarcomere biogenesis start from liquid-liquid phase separation?
Persistence of Mycobacterium tuberculosis in the host is supported by this tagging pathway, making its molecular constituents promising targets for drug development. Our biochemical analysis showed that, although functionally analogous to ubiquitination, pupylation occurs by a chemically distinct pathway involving a different set of enzymes.
We and others recently also showed that Pup can be removed from pupylated proteins by specific cleavage of the isopeptide bond. The existence of a depupylase function suggests roles for pupylation beyond proteasomal degradation.
Nevertheless, design of protein-protein interactions remains a more challenging and less explored task. Moderate success in this area is due to inability of the existing methods to reproduce favorable intermolecular interactions that govern binding of natural proteins.
We developed improved computational methods for design of protein-protein complexes and tested them experimentally in three different systems. In the first example, we convert a promiscuous binder calmodulin into a very specific protein that recognizes a single target. In the second example, we enhance binding affinity of a complex between a synaptic enzyme acetylcholinesterase and its inhibitor fasciculin.
In the third example, we computationally design a de novo binder to Ras, a molecular switch whose loss of function leads to cancer. Our experimental results are fed back into the design procedure, facilitating constant improvement of the computational methodology. One function is related to regulation of mitochondrial transcription while another function is related to mitochondrial ribosome biogenesis.
I will present these new user friendly tools, and discuss how they have enabled exciting new structural results on a variety of problems including integral membrane proteins and, in particular, GPCRs. Photoelectrons are a major source of radiation damage in biological samples.
Experimental results demonstrating the reduction of radiation damage with micron-sized beams will be presented. A new endstation is being developed to provide an intense, highly stable, X-ray beam with a beam size variable between microns. The details of these designs will be presented. Thus one can explore the static ensemble average structure, and more importantly, the time-resolved dynamics of molecules initiated via external perturbations.
In addition, SAXS can be used to determine the arrangement of the components of a macromolecular complex. Micro-crystallographic techniques are often needed to study the most challenging macromolecular complexes because they yield tiny crystals. I will compare and contrast the needs of theses complementary techniques and summarize the state of micro-crystallography beamlines around the world. CIMP crystallization of membrane proteins is a fast screening technology which combines features of the well established classical vapor diffusion experiment with the batch meso phase crystallization, but without premixing of protein and monoolein.
It inherits the advantages of both methods, namely i the stabilization of membrane proteins in the meso phase, ii the control of hydration level and additive concentration by vapor diffusion. CIMP iii significantly simplifies in meso crystallization experiments: It allows the use of standard liquid handling robots suitable for 96 well formats and iv direct monitoring of phase transformation and crystallization events. Friday, 11 January , Add to calendar Fast and accurate calculation of protein-protein interaction: contribution of surface and interface residues Anton Feenstra, VU University Amsterdam, Netherlands Host: Victor Lamzin Seminar Room 48e, EMBL Hamburg show abstract hide abstract Abstract: In many cellular processes physical interactions between proteins play crucial roles; to be functional many proteins must organise into protein complexes, and on the other hand biologically non-functional complexes might give rise to a number of pathologies.
Existing methods for predicting protein-protein interactions PPIs use statistical learning teachniques or other bioinformatic approaches and appear to have limited accuracy. We therefore aim to establish a method based on physical principles using simplified molecular models for computational efficiency, while still maintaining the accuracy of calculating the interactions.
As a second step, we can now perform extensive simulations to assess the contributions of different interface regions to the interaction. We performed random mutations on an equal number of residues in either the surface non-interface , the interface core buried in complex or the interface rim less exposed in complex of two different protein complexes; a TCR-pMHC and an MP1-p15 scaffolding complex.
Our results show that mutations on the interface core lead to less attractive interactions than mutations on the interface rim, while non-interface surface mutations hardly effect the PPI. Furthermore, when we mutate all residues in the interface core into the most likely substitutions excluding self according to BLOSUM, we see no measureable effect on the interaction potential, but if we mutate to the least likely we lose the attractive potential almost completely.
Given the structure of the protein complex, we are now able to calculate an interaction potential between any two proteins in a matter of hours and I will discuss how we are planning to further extend this approach. The contractile filaments, composed of actin and myosin subunits, are crosslinked at the Z-disk and M-band, respectively, to give rise to a lateral assembly of molecular machines with nanometre precision.
In the sarcomeric M-band, the giant ruler proteins titin and obscurin Obsc , its small homologue obscurin-like-1 Obsl1 , and the myosin cross-linking protein myomesin Myom form a ternary complex that is important for the function of the M-band as a mechanical link. These engineered molecular probes allow for determination of the cellular localization of specific proteins and enable signaling events to be followed.
In particular intra-molecular FRET sensors have been successfully constructed that permit one to follow the targets of phosphorylation and calcium dependent protein oligomerisation. Changes in the FRET ratio provide the means to determine both temporal and spatial changes in the activity of enzymes responsible for post-translational modifications, however, the structural basis for these changes remained unclear.
The complex conformational changes that must take place to allow for these sizable 50 - kDa and flexible molecular probes to function as sensors have been determined for the first time using small-angle scattering of x-rays SAXS. The urokinase-type plasminogen activator receptor uPAR is a key component of the plasminogen activation system and plays an important role in cell adhesion.
Consequently it has been targeted for the treatment of disorders involving blood clotting and metastasis in cancer. While crystal structures of uPAR in its active compact form bound to peptides and uPA urokinase plasminogen activator have been determined, the inactive form has so far not been characterised.
We show that a flexible linker between domains 1 and 2 of the receptor is key to the allosteric mechanism linking plasminogen activation to integrin mediated adhesion, and suggest that reducing the flexibility of uPAR may lead to negative therapeutic outcomes.
Schultz, D. A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor uPAR. Structural characterization of proteins and complexes using small-angle X-ray solution scattering. Tuesday, 18 June , Add to calendar Understanding and targeting core metabolic pathways in Mycobacterium tuberculosis: A view from South Africa Valerie Mizrahi , Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa Host: Matthias Wilmanns Seminar room, FLASH hall, EMBL Hamburg show abstract hide abstract Abstract: The emergence and spread of strains of Mycobacterium tuberculosis that are resistant to first and second-line anti-tubercular drugs represents a major global health threat and underscores the urgent need to develop new drugs for tuberculosis, a disease responsible for 9 million new cases and 1.
This need is driving efforts to identify and exploit vulnerable metabolic and biosynthetic pathways in this formidable human pathogen. As a middle-income country that faces an exceptionally severe TB epidemic that has been fuelled by high levels of HIV co-infection, South Africa has a particular responsibility to contribute to global efforts to discover, develop and evaluate new tools for TB control. My laboratory at the University of Cape Town focuses on investigating aspects of the physiology and metabolism of M.
In this talk, I will describe two interrelated studies on cofactor metabolism in M. The intensity integration method EVAL15 is a profile prediction algorithm. It uses a ray-tracing method based on only a small number of physical parameters, mostly the beam size and divergence, the size and shape of the crystal, the wavelength and its dispersion, and the crystals' mosaic spread.
The predicted model profiles are then used for a least-squares fit to the observed data for each reflection, to get the integrated intensities and standard deviations. For less ideal crystals several additional parameters are implemented that account for profiles of reflections that are affected by e. Deconvolution of near overlap in reciprocal space such as in case of multiple lattices or incommensurately modulated crystals is fully implemented. The EVAL software allows extensive monitoring of the integration and data reduction process, very useful in non-standard diffraction data.
Accurate data have been obtained both in small molecule and protein crystallography, in particular for all kind of problematic cases. Nowadays, not only nerds take many gadgets for granted that would have been science-fiction even for Captain Kirk and Mr. However, teleportation machines, spaceships that can travel faster-than-light or holodecks are not yet sold in your local Media Markt or Apple store. Will we ever be able to travel to strange new worlds and beam down to greet strange new civilisations?
Or will our future be limited to watch reruns of Captain Kirk fighting men in lizard suits sitting in our Apple iHolodeck? Yet, many newspapers, radio and tv stations struggle to find the right way of presenting complex scientific research to a broader non-scientific audience. This shows the level of uncertainty within the media about how to deal with and evaluate results of scientific research, which in consequence leads to a lack of publicity, not only for the results but also for the research institutions.
The talk will sketch the way media generate and select the information provided, discuss the criteria which could promote media publicity and outline individual strategies of how to arouse more interest in the scientific results of the future. Crystallogenesis typically traps the most stable low energy states, making it challenging to obtain agonist bound active-state structures of GPCRs.
Stabilization of an active conformation of a GPCR can be achieved in different ways. The most physiologic approach is to use a native signaling partner such as a G protein. An alternative to using a G protein is to identify another binding protein that can stabilize the same conformational state. Antibodies evolved to bind to a diverse array of protein structures with high affinity and specificity.
Such Nanobodies that faithfully mimic the effects of G protein binding were used to obtain diffraction quality crystals and to solve the very first structure of an active agonist-bound state of the human beta2 adrenergic receptor1. One of these nanobodies was used to obtain the high-resolution crystal structure of this complex, providing the first view of transmembrane signaling by a GPCR. Nanobodies are the small 15 kDa and stable single domain fragments harboring the full antigen-binding capacity of the original heavy chain only antibodies that naturally occur in Camelids.
Because of their unique three-dimensional structure, nanobodies have access to cavities or clefts on the surface of proteins. The nanobody platform has the competitive advantage to other recombinant scaffold libraries in that large numbers of fragments harboring the full antigen-binding capacity of genuine in vivo matured antibodies can be screened for high affinity binders in a couple of days, allowing one to fully exploit the humoral response of large mammals against native antigens.
A paramount objective of current research efforts is to address the biology of these molecular machines, by enlisting and developing enabling technologies for their study. An emerging key prerequisite for studying complex biological specimens is their recombinant overproduction. We have designed and validated novel reagents and streamlined protocols for rapidly assembling co-expression constructs for this purpose.
Heterologous expression of eukaryotic proteins and their complexes increasingly necessitate eukaryotic overproduction systems. A polyprotein strategy has been developed to overcome this bottleneck and successfully implemented in our MultiBac baculovirus expression system for producing multiprotein complexes. Friday, 15 November , Add to calendar On the molecular mechanism of antibiotic resistance via multidrug efflux transporters Martin Pos, Goethe-University Frankfurt am Main, Germany Host: Matthias Wilmanns Seminar Room 48e, EMBL Hamburg show abstract hide abstract Abstract: One of the first lines of bacterial defence against antibiotic stress is the deployment of polyspecific membrane transporters to reduce the concentration of these toxic compounds inside the cells.
In Gram-negative bacteria, the establishment of a functional network of membrane efflux transporters including the assembly of secondary three-component efflux systems provides the means for reduction of toxic effects in both cytoplasm and periplasm.
For the major efflux pump system in Escherichia coli, the AcrAB-TolC complex, details on substrate and coupling ion binding at the molecular level have been obtained and provide insight into the coupled process of drug transport energized by the electrochemical gradient of protons across the membrane.
Friday, 7 February , Add to calendar Structural glycobiology of glycosyltransferase complexes Tuomo Glumoff, University of Oulu, Faculty of Biochemistry and Molecular Medicine, Finland Host: Matthias Wilmanns Seminar Room 48e, EMBL Hamburg show abstract hide abstract show tags hide tags Abstract: Correct glycosylation of proteins is fundamentally important in order to maintain crucial cellular functions that include e.
Glycosylation-defective diseases include e. The few human glycosyltransferase structures solved to date are totally neglecting this new concept, and fail to explain how the correct sequence of sugar units and their stereospecific linkages in glycans are determined. Therefore, detailed structural information at atomic resolution of sequentially acting glycosyltransferase heteromeric complexes is needed.
Tags: Structural Biology. We already demonstrated the suitability of MUMBO for flexible ligand docking, homology modeling and crystal structure refinement. In my talk I will present the algorithms currently implemented in MUMBO and discuss the successful redesign of a protein interface as well as the successful transfer of a ligand-binding site onto the serpin anti-chymotrypsin in an ongoing effort to construct a versatile drug delivery shuttle. The evolutionary related V-type ATPases operate in reverse by utilising energy derived from ATP hydrolysis to build up transmembrane ion gradients thereby enabling transport processes across membranes.
A-ATPases are simpler in design than their eukaryotic counterparts, but are more versatile in that they can operate in both directions in dependence of their cellular environment 1. We are using a combination of X-ray structure analysis, electron microscopy and other biochemical and biophysical techniques to obtain a pseudo-atomic model of an A-ATPase 2, 3.
In addition, X-ray structures in different conformations along with normal mode analysis suggest a greater dynamics of the intact complex than previously envisioned which might have implications on cooperativity and regulation of intact rotary ATPases 4, 5. Stewart et al. BioArchitecture 3 2.
Zhou, et al. Science , 3. Lee, et al. Stewart, et al. Nature Communications 3, 5. Current Opinion Structural Biology 25, For the older students aged , the main focus lies on experiments that feature modern research topics and technology such as solid state lasers or optical signal transmission. In addition, scientific talks and lab tours are offered. Together with the theoretical background that we provide, students can understand the physics behind everyday technology.
Thereby they often neglect other things in their life that are also important. This can then influence health, social life and also the work itself. This seminar will deal with the psychological mechanisms leading to a so called "burn-out' and will give some advice to avoid this situation including an optional exercise after the talk for the participants about their own identification with work. One potential application envisages using such pulses for structure determination of materials including biological materials through crystallography experiments, imaging experiments, and small angle x-ray scattering experiments, for both static structure determination and time-resolved structure determination.
The mirror optical systems, detection systems, sample delivery systems and, pending time key, diagnostics will be briefly described. In the second part of this presentation, scientific opportunities for forward scattering experiments will be presented, including opportunities towards single particle imaging experiments. Such models are complex assemblies of concepts, metaphors, stories and other structures that allow us to translate data from many types of instruments to a scale of space and time that we can observe, manipulate, and understand.
Along the way we often remove molecules, cells, and organisms from their natural contexts and place them into simplified, artificial model systems that can be experimentally manipulated. In the process they lose meaning, because the system of complex interactions that links them to their natural environments are interrupted, and they acquire new meaning through the features and environment of the new system. In this talk I will show how language itself behaves like a model system that causes biological entities to lose meaning and acquire meaning.
At the same time it offers tools that function like enzymes, able to break down ideas and recombine them in ways that can be used to explore biological entities and concepts and develop new ways of understanding them. He is the author of the first nine EMBL annual reports and eight popular books on science.
Although he has no formal training in science, he has just published his first scientific paper based on a hypothesis that he developed using the methods that will be introduced in this talk. Solution small angle X-ray scattering SAXS is a rapid method allowing detailed investigation of particle structure and oligomeric composition in solution.
Thanks to new advances for using synchrotron beamlines for biological SAXS, small-sample volumes and rapid data acquisitions are possible. In addition, developments in data analysis have allowed the number of applications to rapidly increase. However, the major bottleneck still remains, which is to obtain sample of sufficient quality. Thereby, the essential challenge is to produce monodisperse samples without any strong interparticle interactions such as aggregations for the accurate extraction of valuable parameters e.
In this respect, the use of an on-line size exclusion chromatography set-up SEC-SAXS can immensely improve sample quality as contaminating components are separated from the sample right before the measurement. In addition, an integrated microsplitter allows for the simultaneous collection of biophysical data. This data is on the one hand essential for the automation of the SEC-SAXS runs as knowledge of the concentration of individual SAXS frames can now be used for the correct normalization of the individual scattering frames.
On the other hand, the overall confidence for interpreting SAXS data is significantly increased with the independently acquired molecular weight estimations of the separated sample components. Other developments include the use of microfluidic devices at the beamline and new advances towards time-resolved SAXS in the submilisecond range.
The idea behind this talk, is not to just demonstrate our new toys but to get you thinking about how these new developments could help you with your own research. However, the structural interpretation of the scattering signals is challenging, while MD simulations frequently suffer from incomplete sampling or from a force field bias. To combine the advantages of both techniques, we present a method that incorporates solution scattering data as a differentiable energetic restraint into explicit-solvent MD simulations, termed SWAXS-driven MD, with the aim to direct the simulation into conformations satisfying the experimental data.
Because the calculations fully rely on explicit solvent, no fitting parameters associated with the solvation layer or excluded solvent are required, and the calculations remain valid at wide angles . The complementarity of SWAXS and MD is illustrated using three biological examples, namely a periplasmic binding protein, aspartate carbamoyltransferase, and a nuclear exportin .
Recent extensions of these methods are discussed. First, towards the interpretation time-resolved anisotropic scattering, and, if time remains, towards Bayesian interpretation of SAXS data. In eukaryotes, Fba also plays a number of non-enzymatic functions. There are two structurally and mechanistically unrelated classes of Fba.
We found that in stationary-phase E. The examples and possible metabolic implication of these findings will be presented in the talk. Several approaches to solving the related problems, including a chemical modification of the enzyme to improve crystal quality, and b computer modeling of a monomer structure to be used as a template for MR, as well as the most recent results in structure characterization, will be introduced.
Tuesday, 28 July , Add to calendar Structure and function of urease: why urea hydrolysis costs two nickels Stefano Luciano Ciurli, Department of Pharmacy and Biotechnology, University of Bologna, Italy Host: Michele Cianci Seminar Room 48e, EMBL Hamburg show abstract hide abstract Abstract: Urease is a nickel-dependent that catalyzes the last step of organic nitrogen mineralization in bacteria, fungi, plants, algae and invertebrates.
The overall hydrolysis of the products generated by urease activity determines an increase of pH of the surrounding milieu, causing negative consequences in medical and agricultural settings. This enzyme represents the main virulence factor for a large variety of ureolytic human pathogens. Furthermore, soil urease activity causes several environmental and economic problems.
In all this instances, a tight control of urease activity is required to counteract its deleterious effects. The structure of the nickel-containing active site cavity has been derived through structural studies on urease from several sources.
These structures revealed a conservation in the coordination environment around the two Ni II ions and suggested a common catalytic mechanism. On the basis of structural information obtained from the crystal structures of native Sporosarcina pasteurii urease and of its complexes with several inhibitors, analogues of the substrate and of the transition state or an intermediate state, a general scheme of the catalytic mechanism of ureases was proposed.
In this mechanism, the nickel-bridging hydroxide acts as the nucleophilic group that attacks the urea molecule bound to the bimetallic nickel cluster by an oxygen atom and a nitrogen atom. These structures are the basis to develop new molecules that could be applied both in medicine and agriculture as urease inhibitors. The structural bases of Ni II sensing through metal-dependent transcription factors will also be described and discussed. Constructed in with a full User program running since , the beamline has seen continuous development ever since.
The beamline adopts an agile, hands on and strategic approach in developing a wide range of hardware and software capabilities most needed by its User community. The beamline s features include flexible experiment capabilities, solution scattering, grazing incidence scattering including reflectivity, low instrument background, highly automated optics, and extensive suite of custom endstation software written within the beamline team.
This talk will highlight key aspects of the beamline that enable a high level of User productivity across a diverse range of disciplines. This talk will include an update on recent and ongoing developments, focusing on aspects which might be useful to other beamlines.
Effector complexes then cleave the invader s genetic material and prevent its replication in the cell. Three types of CRISPR systems have been described that employ different proteins and protein complexes for essentially the same function. We used biochemical and structural studies to determine the mechanistic details of the assembly and function of the Pyrococcus furiosus CMR ribonucleoprotein complex.
Axonal growth cones respond to many guidance cues, which are often expressed in gradients. How growth cones detect concentration gradients, amplify asymmetric signaling and cause turning has not been solved. Our lab showed that Wnt family signaling proteins direct the growth of many classes of neurons in the central nervous system and the highly conserved cell polarity signaling components mediate Wnt-directed axon turning.
I will discuss our latest progress on our understanding of the signaling mechanisms leading to growth cone turning. Carbohydrates such as sialic acid are prominently displayed on many cell surfaces, and they are frequently used by many viruses as their initial, and sometimes only, attachment receptors.
Understanding how viruses engage sialic acid is essential for combating infection and designing improved therapeutic viral vectors. Recent advances in studies of virus-glycan interactions have made it possible to rapidly identify specific receptors using glycan array screening, define the atomic level structure of virus-glycan interactions using crystallography, and generate recombinant viruses or pseudoviruses to rationalize the effect of glycan binding in cell entry, tissue tropism, and disease pathogenesis.
I will report on the current state of our ongoing efforts to define the receptor binding properties of human pathogenic viruses that use sialylated glycan receptors for their cell attachment. In combination with mutagenesis experiments and functional studies, structural analyses have enabled us to understand the determinants of specificity and offer an excellent platform for the development of antiviral agents.
Furthermore, knowledge about glycan binding can also inform the retargeting of viruses to specific tissues, which is important for gene delivery as well as oncolysis. Friday, 23 October , Add to calendar Dielectric study of a lysozyme solution with molecular dynamics simulations: Non thermal effects of low alternating fields Georgios Papadopoulos, University of Thessaly, Greece Host: Dmitri Svergun Seminar Room 48e, EMBL Hamburg show abstract hide abstract Abstract: Constant temperature molecular dynamics simulations have been used to study the dielectric response 10 MHz to GHz of a lysozyme solution using the linear response theory as well as applying weak alternating fields.
The experimental spectra were fully reproduced. Electric field effects on protein's structure and on the dynamics of protein-water hydrogen bonds were revealed as frequency dependent. The key to understanding these processes is to study membrane proteins in a native environment provided by a phospholipid bilayer. Therefore, we are working on the development of phospholipid nanodiscs, a novel detergent-free membrane mimic for structural studies of membrane proteins, and their application to challenging biological systems.
In order to study these systems with NMR and other methods like electron microscopy and X-ray crystallography, we make use of advanced isotope labeling, protein engineering and biochemical methods. One of the first instruments planned at this facility is the NMX macromolecular diffractometer. The NMX instrument is a time-of-flight TOF quasi-Laue diffractometer optimised for small samples and large unit cells in order to locate the hydrogen atoms relevant for the function macromolecules.
The ESS long pulse source with its highly brilliant neutron moderator is ideally suited for a macromolecular diffractometer. More importantly it broadens the range of systems that can be investigated to many biologically very interesting molecules, including membrane proteins such as proton pumps.
The NMX detectors will be mounted on robotic arms, allowing larger unit cells to be resolved by increasing the crystal-to-detector distance. This incurs an increase in the data collection time, but reflections to the same dmin can still be observed by moving the detectors. Many of the scientifically most interesting systems, such as proton pumping membrane proteins, crystallise in large unit cells, so being able to resolve a large unit cell edge is a unique advantage.
The combination of a neutron flux higher than leading high flux reactor instruments, such as LADI-III, together with the ability to resolve large unit cells and the ability to separate signal from background by time-of-flight leads to world-leading performance particularly with the experimentally most challenging systems.
This would transform neutron crystallography into a technique that could answer a significantly larger number of hydrogen related questions in biomolecular science than before. Based on a synchrotron radiation source, it will allow scientist from the Region to access a world-class research infrastructure to boost their research and scientific knowledge.
At the same time its international nature will allow scientists with different cultures, different religions and different experiences to interact with each other. It is therefore an excellent opportunity for the Regional development.
The talk will introduce the organisational structure of SESAME, emphasising how this project is expected to enhance cooperation and mutual comprehension in the Middle East. The current status of the accelerator complex and of beamlines projects will be described. We employ accelerating frequencies two orders of magnitude higher, i. Unlike other omics technologies proteomics can be used to access multiple biological layers including protein-protein interactions, modifications and subcellular localizations.
Our lab has pioneered the technological development of mass spectrometry Beck et al. In our aging society, incurable neurodegenerative disorders such as Alzheimer? Quantitative proteomics can provide a completely new perspective on these? We have developed and applied proteomics tools to better understand the physiological role of neurons by providing the first comprehensive proteome of primary motoneurons Hornburg et al.
We further investigated cardinal features of neurodegeneration such as the mechanism of protein aggregate toxicity in Amyotrophic lateral Sclerosis, Huntington's Disease May et al. I will discuss recent mass spectrometry developments and applications that led to novel insights into the mechanisms of neurodegeneration and will outline how mass spectrometry can contribute to future research.
If experimental phasing is performed with the weak anomalous signal of inherent sulfur atoms in a protein, high multiplicity is required. As radiation damage and multiplicity are in conflict with each other, the question is: when is the point reached, where adding data will lead to a worse result? This will be discussed based on sulfur SAD experiments performed on thaumatin at P The scanning serial data collection technique is applied in-situ for data collection on membrane proteins crystallized in meso-phase.
Recent improvements of X-ray optics delivered optimal conditions for structure determination of large macromolecular complexes. This will be exemplified by crystal structures of the native human 20S proteasome and its complexes with inhibitors, which either represent drugs approved for the treatment of cancer or are in clinical trials for this purpose, at unprecedented resolutions up to 1. The structures reveal atomic details of inhibition mechanisms and enable next-generation inhibitor design.
P13 is tunable across the energy range from 4 to Data collections at energies as low as 4 keV 3. At high energies, the high photon flux 5. Automated sample mounting is available by means of the robotic sample changer 'MARVIN' with a duty-cycle of less than one minute and a dewar capacity of samples. In close proximity to the beamline, laboratories have been set up for sample preparation and characterization; a laboratory specifically equipped for on-site heavy atom derivatization with a library of more than compounds is available to beamline users.
The capabilities of the beamline are demonstrated by examples of sulphur-SAD phasing enabled by X-ray beams adjusted optimally both in terms of beam size and X-ray energy and by successful structure solutions from small crystals. On one hand we develop and utilize high-throughput quantitative approaches that reveal functional interactions between genes at a whole cell level. On the other hand, we zoom into these networks to understand how different functional modules are interconnected, often at a detailed mechanistic level.
Here I will present how we use such approaches to shed light into gene function and pathway organization, to understand the action of drugs and their interplay when combined, and to probe how protein machineries operate at the bacterial cell envelope- how they are organized, how they coordinate their actions and how the cell senses when they are malfunctioning.
We have also recently moved our approaches to the host-pathogen interface and the dynamic microbial communities formed in our gut. Our main goals are to: a elucidate pathways Salmonella uses to hijack its host machinery and b to probe how gut microbial communities are formed, how they react to nutrition and pharmaceuticals, and how their composition and characteristics affects our health.
Some are detrimental to human development, whereas those targeting pathogenic bacteria or crop pathogens can be beneficial for us. An integral part of icosahedral viruses is the capsid protein shell protecting the genome. Concurrent Session Impact of climate change and electricity market liberalization on hydropower plants with reservoir. Concurrent Session Self generation and payment for service reliability in Nigeria. Concurrent Session Fossil fuel subsidies as a lose-lose: fiscal and environmental burdens in Turkey.
Concurrent Session Oil and unemployment in a new-Keynesian Model. Concurrent Session Energy efficiency saving, rebound effects and the impact of energy policy instruments: evidence from EU countries. Concurrent Session Battery vs hybrids? Future perspectives of electric vehicles. Concurrent Session An analysis on price formation in Turkish electricity market.
Concurrent Session Euro-Mediterranean cooperation on renewable energy finance. Concurrent Session Barriers to households investment in energy efficiency and renewables — evidence from the OECD survey on household environmental behaviour and attitudes. Concurrent Session A top-down scenario quantification methodology for electricity highways at Concurrent Session Socioeconomic impact of the renewables: the effect on the regional structuring. Concurrent Session Energy access: feeding of isolated areas with no local energy resources.
Concurrent Session The effect of financial incentives in promoting wind energy in Turkey. Concurrent Session Testing the international crude oil market integration with structural breaks. Concurrent Session Oil price shocks and the effect on the price of other commodities.
Concurrent Session Model based analysis of a massive development of electric vehicle in the Paris Ile de France region. Concurrent Session A regional demand forecasting study for transportation fuels in Turkey.
Concurrent Session Normalizing residential and commercial energy demand for climatic conditions. Concurrent Session On the link between using low carbon fuels and energy efficiency improvements for attaining greenhouse gas emissions reduction goals.
Concurrent Session Information feedback effects in retail electricity markets. Concurrent Session Carbon pricing and distributional effects on firms: a methodological survey. Concurrent Session Operational costs of the Spanish electricity system: a demand or supply effect? Concurrent Session Macroeconomic impacts of regional climate change adaptation strategies. Concurrent Session Probabilistic welfare analysis for system adequacy analytical insights.
Concurrent Session Smart grid and demand response: a generators-centered approach in the current European context. Concurrent Session Transparency and bidding behavior in electricity wholesale markets. Concurrent Session Flexible and integrated: photovoltaic investment evaluation in a Smart Grid environment.
Concurrent Session Participatory decision support for power systems planning: empirical findings from a case study in the context of the German energy transition. Concurrent Session How to support energy efficiency — an experimental investigation of individual preferences. Concurrent Session Effect of dynamic electricity transmission tariffs on investment allocation.
Concurrent Session Integrated power transmission and generation expansion planning — a model formulation for Germany in Concurrent Session Evaluating the energy savings effects of a utility DSM program using a difference-in-difference coarsened exact matching approach. Concurrent Session The impact of support schemes applied for electricity produced from renewable energy sources on electricity prices in the Baltic States. Concurrent Session The impact of the policy mix for renewable power generation technologies on invention: a patent analysis for Germany.
Concurrent Session Promoting renewable energies in the Mena region: regulatory developments and possible interactions with future eu support schemes for RES-E. Concurrent Session Energy consumption and efficiency in the EU stock of shopping malls. Concurrent Session Increased electricity demand flexibility enabled by smart grid: impacts on prices, security of supply and revenues in Northern Europe.
Concurrent Session Optimal design for hourly electricity price in the Italian Market. Preliminary results. Concurrent Session Effects of energy prices on economic growth. Concurrent Session Energy security indicators: are they helpful in assessing policies addressing energy security?
Concurrent Session Modelling the flex-offer as a commodity. Concurrent Session Integration of offshore wind energy into the grid system in Germany- modeling of a market oriented prevision. Concurrent Session Large-scale land acquisitions in Africa. Exploring players, roles and responsibilities. Concurrent Session Economics for flexible consumers in balancing markets. Concurrent Session Reaping the carbon rent: abatement and overallocation profits in the European cement industry, insights from an LMDI decomposition.
Concurrent Session Why is spot carbon so cheap and future carbon so dear? The term structure of carbon prices. Concurrent Session Is policy mix consistency a necessary but not sufficient condition for technological change in renewable power generation technologies? Concurrent Session Investigating the degrowth paradigm through prospective modeling: the case of France.
Concurrent Session Regulatory barriers to energy storage technologies. Concurrent Session Flexibility in competitive electricity markets. Concurrent Session Could a real level-playing field in middle European electricity markets by a full internalization of environmental costs trigger the required energy transition? Concurrent Session Can renewable energy energise remote Australian communities?
Concurrent Session What are the costs and benefits associated to Renewable Energies deployment in Spain? Evidence for the period Concurrent Session Environmental impacts of the French final consumption. Concurrent Session A carbon Kuznets curve with oil prices: the Spanish case. Concurrent Session Working progress of Italian position in to framework of set plan. Concurrent Session The renewable vs. Concurrent Session Second raw materials: packaging recovery.
Concurrent Session Banning non-conventional oil extraction: would a unilateral move of the EU really work? Concurrent Session An unorthodox way of reducing public debt burden: the potential role of renewable energy. Concurrent Session Microgrids and pricing of electricity. Concurrent Session Risk management and portfolio optimization for gas-and coal-fired power plants in Germany: a multivariate garch approach.
Concurrent Session Measuring the impact of existing environmental regulations and fiscal legislations on the European road transport demand: a dynamic panel data econometric analysis. Concurrent Session Land-use competition between energy and food — the case of climate change mitigation Ireland. Concurrent Session Energy efficiency and the rebound: estimating income and substitution effects. Concurrent Session The role of independent regulation in the relationship of power tariff and election.
Concurrent Session The value of better wind information. Concurrent Session Adaptation to climate change and US residential energy use — does adaptation reduce greenhouse gas emissions? Concurrent Session Carbon tax, pensions and public deficits: the hidden cost of the compartmentalization of expertise.
Concurrent Session A functional efficiency index of energy futures markets. Concurrent Session Seller density and retail prices: empirical evidence from the Spanish automotive fuel market. Concurrent Session Understanding the evolution of global energy use. Concurrent Session Economic development and pollution leakage. Concurrent Session Calculation of the maximum commercial border capacity in interconnected gas networks.
Concurrent Session Estimating fluctuations in oil and gas investments. Concurrent Session The role for Power-to-Gas in future energy systems: a model-based assessment for the Netherlands. Concurrent Session Assessment of the magnitude and location of socio-economic benefits of Spanish biofuel production.
Concurrent Session The role of curtailment in dealing with the variability of renewables. Concurrent Session Development and assessment of mitigation climate change policy portfolios for Estonia. Concurrent Session Variable Renewable Energies and storage development in long term energy modeling tools. Concurrent Session Generation adequacy outlook in a bipolar electricity system. Electricity supply security assessment for Belgium up to Concurrent Session Modeling and forecasting the short run electricity demand: a comparison of econometric methods for EU and Latam countries.
Concurrent Session Energy manager as an obligation for large end users: the Italian experience. Concurrent Session Territorial open data to support seap development. Concurrent Session Benefits of incorporating non-energy and non-CO2 processes into energy systems models. Concurrent Session Energy consumption and poverty reduction in Africa. Concurrent Session Climate policy analysis with sectoral targets for the steel sector. Concurrent Session Two price zones in the German electricity market — distributional effects of regional price signals.
Concurrent Session Peak-load pricing with different types of dispatchability. Concurrent Session Petroleum taxation and investment behaviour. Concurrent Session About business model specifications of a smart charging manager to integrate electric vehicles into the German electricity market. Concurrent Session Abuse of dominance in vertically disintegrated gas markets. Concurrent Session Assessment of levelized economics of fossil-fuel-based polygeneration energy systems.
Concurrent Session Techno-economic modeling and analysis of cogeneration units in France. Concurrent Session Managing investor and consumer exposure to electricity market price risk through: feed in tariff design. Concurrent Session Europe, Ukraine and Russian gas: could the crisis in Ukraine threaten the security of Europe's energy supply?
Concurrent Session Solar photovoltaics in Brazil: adressing the chasm preventing the deployment of its DG generation. Concurrent Session The renewables influence on market splitting: the Iberian spot electricity market. Concurrent Session Investment planning and optimization of urban and rural hybrid energy systems. Concurrent Session Intra-sectoral efficiency gains vs delocalization: a decomposition analysis of global energy intensity between and Concurrent Session From fuel taxation to efficiency standards: a wrong turn in European climate protection?
Concurrent Session A study of the actual conditions of renewable energy use in Japanese municipalities. Concurrent Session The effect of fluctuations in natural gas prices on competition in oligopolistic electricity markets. Concurrent Session How do capacity markets affect demand flexibility: welfare effects of dynamic capacity pricing in the presence of high shares of fluctuating renewable resources.
Concurrent Session Balancing forecast errors in continuous-trade intraday markets. Concurrent Session Impact of the flexibility in the international carbon credits market on the European allowances price. Concurrent Session Life cycle assessment of waste to energy plant with and without carbon dioxide capture technology.
Concurrent Session Cost-minimal investments into generation capacities in Europe given a Europe-wide renewables policy. Concurrent Session Fundamental drivers of regime-switching: an analysis of German power prices. Concurrent Session Energy and chaos: modeling energy in a dynamics growth model with chaotic bifurcation. Concurrent Session The gainers and losers of global warming: implications for adaptation and mitigation.
Concurrent Session The impact of uncertainty on the European energy market: a scenario aggregation approach. Kittelsen , Stein W. Concurrent Session Fostering renewables and recycling a carbon tax: joint aggregate and intergenerational redistributive effects. Concurrent Session Power plant investments under uncertainty - a linear mean risk model for selecting efficient power plant portfolios.
Concurrent Session Assessment of industrial power prices. Concurrent Session Micro auctions for distributed generation with flexible zones. Energy supply security assessment for Belgium up to Concurrent Session An efficient assessment of capacity mechanisms in electricity market. Concurrent Session Integrating larger shares of intermittent renewables into the electricity system: competitive or centrally planned? Concurrent Session Carbon divestment as rational climate policy measure? Concurrent Session Inefficiencies of grid regulation - the case of blackouts in electricity grids.
Concurrent Session Outlook of the Japanese economy and energy supply-demand structure toward Concurrent Session Assessing the disruptive potential of new technologies in the European energy market. Concurrent Session Assessing dynamic effects of capacity remuneration mechanisms on generation investment: comparison between strategic reserve mechanism and capacity market. Concurrent Session Diversity of the means of natural gas purchase.
Concurrent Session Residential bottom-up load modelling with price elasticity. Concurrent Session Long-term modelling of power-to-gas capacity developments and operation in the German power system. Concurrent Session Quantum Leap - why and how energy utilities aim to servitize their business models. Concurrent Session Economic curtailment of renewable energy sources. Concurrent Session Structural similarity and dependency of research networks in the German PVindustry— Does the comprehensiveness of the policy mix matter?
Concurrent Session On the ambiguous market prospects of storages for promoting electricity generation from intermittent renewables. Concurrent Session Opportunity cost of reactive power provision. Concurrent Session Ten propositions on electricity market design: energy-only vs. Concurrent Session Energy productivity: aligning global agendas. Concurrent Session RES load diagram analyses - step towards virtual power plant.
Concurrent Session Determinants of energy-efficient investments in Slovenian manufacturing industries. Concurrent Session Impact of the optimal energy mix with renewable risk on industrial greening. Concurrent Session An analysis of household energy consumption in Taiwan: evidence from quantile regression. Concurrent Session Adjusting the electricity consumption: consumer's option to choose.
Concurrent Session Electricity derivative markets and Samuelson hypothesis. Concurrent Session Wind Power Deployment: the role of public participation in decision-making process. Concurrent Session Mode choices of transport to work in Switzerland. Concurrent Session How dependent is growth from primary energy? An assesment for OECD countries. Concurrent Session Interplay between electricity and transport sectors — Integrating the Swiss car fleet and electricity system.
Concurrent Session The impact of shale gas on the costs of climate policy. Concurrent Session The EU emission trading scheme: first evidence on phase 3. Concurrent Session Exploring transaction costs in passive house-oriented retrofitting. Sverre A. Concurrent Session The global economic long-term potential of modern biomass in a climate constrained world.
Concurrent Session Peak demand and time-of-use pricing in a field study of residential electricity demand in Germany. Concurrent Session A new approach for biomass potential determination — a case study for the Czech Republic. Concurrent Session Real-time price elasticity of electricity demand in wholesale markets. Concurrent Session Reform potentials for congestion management in European electricity networks. Concurrent Session Conventional power system flexibility in Germany. Concurrent Session Analysis for extensive integration of variable renewables with dynamic multiregional optimal power generation mix model.
Concurrent Session Forecast of energy-related carbon dioxide emissions in Lithuania. Concurrent Session Modeling concept for renewable energy expansion and interaction in Europe: the case of Germany and Greece. Concurrent Session Integrating renewable energy in power systems: challenges and solutions. Concurrent Session Smart city Hartberg: smart city development on small-town scale.
Concurrent Session Cost estimation of existing German renewable energy installations in the current support mechanism till Concurrent Session Social preferences and political support for Germany's energy turnaround: an experimental study of consumer behavior. Concurrent Session A dynamic approach of the fuel poverty phenomenon. Concurrent Session The role of nuclear power in sustainable low-carbon electricity systems. Concurrent Session Smart meters, efficiency gains and economy-wide rebound effects.
Concurrent Session EU climate and energy policy beyond Are additional targets and instruments for renewables economically reasonable? Concurrent Session Who benefits from renewables? Economic impacts of renewable energy along the value chain and value creation policies. Concurrent Session Construction of hybrid input-output tables for E3 CGE model calibration and consequences on energy policy analysis.
Concurrent Session The impact assessment of various carbon tax rate on the economy and CO2 emission of Taiwan. Concurrent Session Understanding the interactions between global and regional seasonality of crude oil consumption. Concurrent Session The use of renewable energy cooperation mechanism: evidence from hydropower projects in Norway. Concurrent Session Quantifying the impact of wind power generation in day-ahead market: the case of Denmark. Concurrent Session On the impact of market concentration on investment decisions and security of supply in electricity markets — an agent-based analysis.
Concurrent Session New cross-border balancing arrangements in Europe: what are the efficiency gains and who reaps them? Concurrent Session Comparative statics for real options on oil: what stylized facts to use? Concurrent Session Energy price volatility: the link between fossil energy and woody bioenergy.
Concurrent Session Energy reference forecast and energy policy targets for Germany. Concurrent Session Willingness-to-pay for alternative fuel vehicle characteristics: a stated choice study for Germany. Concurrent Session Modeling resource use with endogenous time preference and minimum consumption requirement.
Concurrent Session Measuring the efficiency of energy-intensive industries across 23 EU countries. Concurrent Session Modeling the integration of variable renewable energies VRE into the electrical grid in the witch model: techno-economic impacts of different approaches. Concurrent Session Changes of the Italian energy system from to with particular reference to the industrial sector: implications for the future.
Concurrent Session A Markov-Switching approach to modeling the asymmetric price transmision: an application for the Spanish fuel market. Concurrent Session Reliability option contracts: the effect of the explicit penalty on the merit order of the auction. Concurrent Session Oil and debts: are they substitutes? Concurrent Session Analyzing scale effects of energetic autarky with an economic capacity and dispatch optimization model. Concurrent Session Households facing constraints.
Fuel poverty put into context. Concurrent Session The role of regions and provinces to support the participation of small local authorities in the Covenant of Mayors. Concurrent Session Market power rents and climate change: a rationale for export taxes on coal? Concurrent Session The influence of individual wind feed-in time series on electricity spot market prices and their effect on the economic evaluation of storage systems.
Concurrent Session Innovative device for control of electric energy consumption. Concurrent Session Regional gas market integration in the changing geopolitical landscape. Concurrent Session Vertical integration and the valuation of international oil companies. Concurrent Session A two stage energy planning model integrating power expansion and regional energy systems for the assessment of solar and CGS.
Concurrent Session Dynamic modelling of cost systems applied to energy transition. Concurrent Session Energy-efficient innovation a response to market -based incentives? Concurrent Session Distribution grid monitoring through pilot injection and successive interference cancellation. Concurrent Session Long term scenario for an energy transition in the French transportation sector under multiple policy objectives. Concurrent Session Equilibrium pricing of reserve power.
Concurrent Session An analysis on changes in economics of smart house using photovoltaic cell and electricity storage system. Concurrent Session Exploring barriers to company adoption of load shift. Concurrent Session Quantitative analysis of the merit order effect from photovoltaic production in key European countries and effect of market coupling. Concurrent Session Rig services and taxation. Concurrent Session Encouraging hydro-solar complementarity in the Swiss electricity market.
Concurrent Session Analysis of the German border power transmission lines and congestion management as an element towards a single European electricity market. Concurrent Session Gross employment from renewable energy in Germany. Concurrent Session Value of flexibility for balancing wind power generation.
Concurrent Session An analysis of the allocation and costs of risk under different renewable support instruments. Concurrent Session A systematic mapping and evaluation of barriers and benefits of the demand side resource participation in electricity markets.
Concurrent Session A comparison of new energy technology competitiveness index by countries. Concurrent Session The effect of renewable subsidy schemes and market design on the spatial distribution of wind energy installation. Concurrent Session In a world without support schemes: investments in wind power by the energy-only market.
Concurrent Session Dynamics of industrial consolidation in the EU27 electricity and gas industry Concurrent Session Power sector decarbonization — which technologies matter? Concurrent Session The oil-growth nexus in oil producers: macro panel evidence. Concurrent Session Evolve or die: new bidding strategies for combined cycle electricity plants after the introduction of renewable energy.
Concurrent Session The probability of long phases of very high and low wind power feed-in and residual load. Concurrent Session Mechanisms for generating capacity expansion and power market structures: Russian case study.
Concurrent Session Emission payments and sustainability criteria for solid wood biomass: optimal energy mix and costs of targets. Concurrent Session A fast method for generation-park-development analysis.
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