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"Downhill folding is a process in which a protein folds without encountering any significant macroscopic free energy barrier. It is a key prediction of the folding funnel hypothesis of the energy landscape theory of proteins. Overview Downhill folding is predicted to occur under conditions of extreme native bias, i.e. at low temperatures or in the absence of denaturants. This corresponds to the type 0 scenario in the energy landscape theory. At temperatures or denaturant concentrations close to their apparent midpoints, proteins may switch from downhill to two-state folding, the type 0 to type 1 transition. Global downhill folding (or one-state folding) is another scenario in which the protein folds in the absence of a free energy barrier under all conditions. In other words, there is a unimodal population distribution at all temperatures and denaturant concentrations, suggesting a continuous unfolding transition in which different ensembles of structures populate at different conditions. This is in contrast to two-state folding, which assumes only two ensembles (folded and unfolded) and a sharp unfolding transition. Free energy barriers in protein folding are predicted to be small because they arise as a result of compensation between large energetic and entropic terms. Non-synchronization between gain in stabilizing energy and loss in conformational entropy results in two-state folding, while a synchronization between these two terms as the folding proceeds results in downhill folding. Experimental studies Transition state structures in two- state folding are not experimentally accessible (by definition they are the least populated along the reaction coordinate), but the folding sub-ensembles in downhill folding processes are theoretically distinguishable by spectroscopy. The 40-residue protein BBL, which is an independently folding domain from the E2 subunit of the 2-oxoglutarate dehydrogenase multi-enzyme complex of E. coli, has been experimentally shown to fold globally downhill. Also, a mutant of lambda repressor protein has been shown to shift from downhill to two-state upon changing the temperature/solvent conditions. However, the status of BBL as a downhill-folding protein, and by extension the existence of naturally occurring downhill folders, has been controversial. The current controversy arises from the fact that the only way a protein can be labeled as two-state or downhill is by analyzing the experimental data with models that explicitly deal with these two situations, i.e. by allowing the barrier heights to vary. Unfortunately, most of the experimental data so far have been analyzed with a simple chemical two-state model. In other words, the presence of a rather large free energy barrier has been pre-assumed, ruling out the possibility of identifying downhill or globally downhill protein folding. This is critical because any sigmoidal unfolding curve, irrespective of the degree of cooperativity, can be fit to a two-state model. Kinetically, the presence of a barrier guarantees a single-exponential, but not vice versa. Nevertheless, in some proteins such as the yeast phosphoglycerate kinase and a mutant human ubiquitin, non-exponential kinetics suggesting downhill folding have been observed. A proposed solution to these problems is to develop models that can differentiate between the different situations, and identify simple but robust experimental criteria for identifying downhill folding proteins. These are outlined below. Equilibrium criteria Differences in apparent melting temperatures An analysis based on an extension of Zwanzig's model of protein folding indicates that global downhill folding proteins should reveal different apparent melting temperatures (Tms) when monitored by different techniques. This was experimentally confirmed in the protein BBL mentioned above. The unfolding followed by differential scanning calorimetry (DSC), circular dichroism (CD), fluorescence resonance energy transfer (FRET) and fluorescence all revealed different apparent melting temperatures. A wavelength-dependent melting temperature was also observed in the CD experiments. The data analyzed with a structure-based statistical mechanical model resulted in a unimodal population distribution at all temperatures, indicating a structurally uncoupled continuous unfolding process. The crucial issue in such experiments is to use probes that monitor different aspects of the structure. For example, DSC gives information on the heat capacity changes (and hence enthalpy) associated with unfolding, fluorescence on the immediate environment of the fluorophore, FRET on the average dimensions of the molecule and CD on the secondary structure. A more stringent test would involve following the chemical shifts of each and every atom in the molecule by nuclear magnetic resonance (NMR) as a function of temperature/denaturant. Though time-consuming, this method does not require any specific model for the interpretation of data. The Tms for all the atoms should be identical within experimental error if the protein folds in a two-state manner. But for a protein that folds globally downhill the unfolding curves should have widely different Tms. The atomic unfolding behavior of BBL was found to follow the latter, showing a large spread in the Tms consistent with global downhill behavior. The Tms of some atoms were found to be similar to that of the global Tm (obtained from a low-resolution technique like CD or fluorescence), indicating that the unfolding of multiple atoms has to be followed, instead of a few as is frequently done in such experiments. The average atomic unfolding behavior was strikingly similar to that of CD, underlining the fact that unfolding curves of low resolution experiments are highly simplified representations of a more complex behavior. Calorimetry and crossing baselines Baselines frequently used in two-state fits correspond to the fluctuations in the folded or unfolded well. They are purely empirical as there is little or no information on how the folded or unfolded states' property changes with temperature/chemical denaturant. This assumes even more importance in case of DSC experiments as the changes in heat capacity correspond to both fluctuations in the protein ensemble and exposure of hydrophobic residues upon unfolding. The DSC profiles of many small fast- folding proteins are broad, with steep pre-transition slopes. Two-state fits to these profiles result in crossing of baselines indicating that the two- state assumption is no longer valid. This was recognized by Munoz and Sanchez- Ruiz, resulting in the development of the variable-barrier model. Instead of attempting a model-free inversion of the DSC profile to extract the underlying probability density function, they assumed a specific free energy functional with either one or two minima (similar to the Landau theory of phase transitions) thus enabling the extraction of free energy barrier heights. This model is the first of its kind in physical biochemistry that enables the determination of barrier heights from equilibrium experiments. Analysis of the DSC profile of BBL with this model resulted in zero barrier height, i.e. downhill folding, confirming the earlier result from the statistical mechanical model. When the variable-barrier model was applied to a set of proteins for which both the rate and DSC data are available, a very high correlation of 0.95 was obtained between the rates and barrier heights. Many of the proteins examined had small barriers (<20 kJ/mol) with baseline crossing evident for proteins that fold faster than 1 ms. This is in contrast to the traditional assumption that the free energy barrier between the folded and unfolded states are large. Simulations Because downhill folding is difficult to measure experimentally, molecular dynamics and Monte Carlo simulations have been performed on fast-folding proteins to explore their folding kinetics. Proteins whose folding rate is at or near the folding "speed limit", whose timescales make their folding more accessible to simulation methods, may more commonly fold downhill. Simulation studies of the BBL protein imply that its rapid folding rate and very low energy barrier arise from a lack of cooperativity in the formation of native contacts during the folding process; that is, a low contact order. The link between lack of cooperativity and low contact order was also observed in the context of Monte Carlo lattice simulations These data suggest that the average number of "nonlocal contacts" per residue in a protein serves as an indicator of the barrier height, where very low nonlocal contact values imply downhill folding. Coarse-grained simulations by Knott and Chan also support the experimental observation of global downhill folding in BBL. See also * Dr. Victor Muñoz References Further reading * Bieri O, Kiefhaber T. (2000). Kinetic models in protein folding. In Mechanisms of Protein Folding 2nd ed. Ed. RH Pain. Frontiers in Molecular Biology series. Oxford University Press: Oxford, UK. * Gruebele M. (2008) Fast protein folding. In Protein Folding, Misfolding and Aggregation Ed. V Muñoz. RSC Biomolecular Sciences series. Royal Society of Chemistry Publishing: Cambridge, UK. Category:Protein structure Category:Statistical mechanics "
"A microcontroller development board (Arduino Duemilanove), which could be used for embedded systems development. Electrical/Electronics engineering technology (EET) is an engineering technology field that implements and applies the principles of electrical engineering. Like electrical engineering, EET deals with the "design, application, installation, manufacturing, operation or maintenance of electrical/electronic(s) systems." However, EET is a specialized discipline that has more focus on application, theory, and applied design, and implementation, while electrical engineering may focus more of a generalized emphasis on theory and conceptual design. Electrical/Electronic engineering technology is the largest branch of engineering technology and includes a diverse range of sub-disciplines, such as applied design, electronics, embedded systems, control systems, instrumentation, telecommunications, and power systems. Education Accreditation The Accreditation Board for Engineering and Technology (ABET) is the recognized organization for accrediting both undergraduate engineering and engineering technology programs in the United States. Coursework EET curricula can vary widely by institution type, degree type, program objective, and expected student outcome. Each year after, however, ABET publishes a set of minimum criteria that a given EET program (either associate degree or bachelor's degree) must meet in order to maintain its ABET accreditation. These criteria may be classified as either general criteria, which apply to all ABET accredited programs, or as program criteria, which apply to discipline-specific criteria. Associate degree Associate degree programs emphasize the practical field knowledge that is needed to maintain or troubleshoot existing electrical/electronic systems or to build and test new design prototypes. Discipline-specific program outcomes include the application of circuit analysis and design, analog and digital electronics, computer programming, associated software, and relevant engineering standards Coursework must be at a minimum algebra and trigonometry based. Bachelor's degree Bachelor's degree programs emphasize the analysis, design, and implementation of electrical/electronic systems. Some programs may focus on a specific sub-discipline, such as control systems or communications systems, while others may take a broader approach, introducing the student to several different sub-disciplines. Math to differential equations is a minimum requirement for ABET accredited bachelor's level EET degrees. In addition, graduates must demonstrate an understanding of basic project management skills. The United States Department of Commerce classifies the bachelor of science in electrical engineering technology (BSEET) as a STEM undergraduate engineering degree field. In many states, recent graduates and students who are close to finishing an undergraduate BSEET degree are qualified to sit-in for the Fundamentals of Engineering exam while those BSEETs who have already gained at least four years’ post-college experience are qualified to sit-in for the Professional Engineer exam for their licensure in the United States. The importance of the licensing board requirements depend upon location, level of education, required years of experience, and the BSEETs sub-discipline are the passageways for becoming a licensed engineer. The knowledge obtained by a TAC/ABET accredited program is one pathway that may help students prepare for and pass the FE/PE exam. For example, in the United States and Canada, "only a licensed engineer may seal engineering work for public and private clients". Career Graduates of electrical/electronics engineering technology programs work in a wide range of career fields. Some examples include: *Engineering management *Telecommunications *Signal processing *Medical technology and devices *Instrumentation *Integration Engineer *Control *Aerospace and avionics *Computers *Electrical power industry and power distribution *Optics and Optoelectronics *Manufacturing and manufacturing test engineer *Marine Engineering *Research and development *Project management and Operations research *Supervision/Management *Systems analyst *Technology management Associate degree Electrical/electronic engineering technicians may have a two-year associate degree and considered craftsman technicians. Eventually, with additional experience and certifications obtained then the craftsman technicians may advance to master craftsman technicians. Bachelor degree Electrical/electronic engineering technologists are broad specialists, rather than central technicians. EETs have a bachelor's degree and are considered applied electrical or electronic engineers because they have electrical engineering concepts to use in their work. Entry-level jobs in electrical or electronics engineering generally require a bachelor's degree in electrical engineering, electronics engineering, or _electrical engineering technology_. See also *Outline of engineering *IEEE *Applied science *Mechanical engineering technology *Computer engineering *Manufacturing engineering References External links *IEEE Global History Network A wiki-based site with many resources about the history of IEEE, its members, their professions and electrical and informational technologies and sciences. Category:Technology by type Category:Electrical engineering "
"Waterwitch, water-witch, Water Witch, or variant, may refer to: Ships *, a Confederate States Navy gunboat *, several Royal Navy vessels *, several United States Navy ships *Water Witch (schooner), an 1832 ship that sank in Lake Champlain in 1866 *Water Witch (1835 cutter), a cutter owned by the Government of South Australia *Water Witch (1835 steamer), a British Cross- Channel steam packet Other uses *Waterwitch, New Jersey, an unincorporated community in Highlands, Monmouth County *The Water-Witch, an 1830 novel by James Fenimore Cooper *Water Witch (novel) a novel by Connie Willis and Cynthia Felice *Dowsing, divination to find ground water or other minerals *Pied-billed grebe, a species of waterfowl sometimes referred to as Water Witch See also * Witch (disambiguation) * Water (disambiguation) "