It is generally accepted that the information necessary to specify the native, functional, three-dimensional structure of a protein is encoded entirely within its amino acid sequence; however, efficient reversible folding and unfolding is observed only with a subset of small single-domain proteins. Refolding experiments often lead to the formation of kinetically-trapped, misfolded species that aggregate, even in dilute solution. In the cellular environment, the barriers to efficient protein folding and maintenance of native structure are even larger due to the nature of this process. First, nascent polypeptides must fold in an extremely crowded environment where the concentration of macromolecules approaches 300-400 mg/mL and on average, each ribosome is within its own diameter of another ribosome (1-3). These conditions of severe molecular crowding, coupled with high concentrations of nascent polypeptide chains, favor nonspecific aggregation over productive folding (3). Second, folding of newly-translated polypeptides occurs in the context of their vehtorial synthesis process. Amino acids are added to a growing nascent chain at the rate of {approx}5 residues per set, which means that for a 300 residue protein its N-terminus will be exposed to the cytosol {approx}1 min before its C-terminus and be free to begin the folding process. However, because protein …

It is peculiar that in situ hybridization (ISH), a technique with many similarities to immunohistochemistry (IHC), has not enjoyed the phenomenal growth in both basic research and clinical applications as has its sister technique IHC. Since the late 1970s, when immunoperoxidase techniques began to be applied to routine diagnostic material and to numerous research applications, there has been a natural evolution of the IHC procedure. Namely, only a few primary antibodies were available commercially at the onset, and only one indirect and the peroxidase-antiperoxidase (PAP) technique detection systems were in place. With the advent of avidin-biotin detection systems and monoclonal antibodies, and a viable commercial market, extraordinary growth of the procedure's applications in clinical research and diagnostic pathology occurred during the subsequent two decades. Today, IHC is automated and widely used for research purposes and, to a large extent, has become a routine diagnostic ''special stain'' in most clinical laboratories. During the same period, ISH enjoyed very little growth in both research and diagnostic applications. What has accounted for this lack of maturation of the technique? The success of IHC is part of the reason measuring a gene's encoded protein routinely and inexpensively, particularly as automation evolved, rendered IHC a …

This report assesses steam generation and use in the pulp and paper, chemical, and petroleum refining industries, and estimates the potential for energy savings from implementation of steam system performance and efficiency improvements.

The p53 tumor suppressor is a tetrameric transcription factor that is post-translational modified at {approx}18 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review the posttranslational modifications to p53 and the pathways that produce them in response to both genotoxic and non-genotoxic stresses.

For many applications, silver salt-based autometallography (often also called silver enhancement or silver development) is required to visualize colloidal gold (1-5 nm in diameter) or the small 1.4 nm Nanogold{reg_sign} particles (Nanoprobes, Yaphank, NY, USA). Although even Nanogold may be seen directly by scanning-transmission electron microscopy (STEM), by transmission EM (TEM; in thin sections without stain or ice-embedded cryo-EM samples), energy filtered TEM, and scanning EM (SEM), silver enhancement makes viewing in the EM more facile since the particles are enlarged to approximately 10 to 20 nm, convenient for most specimens. Autometallographic (AMG) enhancement is required in order to visualize smaller gold particles such as Nanogold for light microscopy (LM) or in blots or gels. This chapter includes the following protocols: Protocol for HQ silver enhancement of Nanogold; Protocols for use of silver-enhanced Nanogold with osmium tetroxide--(A) Procedure using reduced concentration of OsO{sub 4}; (B) Procedures for gold toning; Protocol for HQ silver enhancement of Nanogold in pre-embedding immunocytochemistry for cell cultures; Protocol for gold enhancement of Nanogold for EM; Protocol for gold enhancement of Nanogold for LM; Protocol for staining blots with Nanogold and silver enhancement; and Protocol for staining gels with Nanogold and silver enhancement.

Nanogold{reg_sign}, a gold cluster with a core of gold atoms 1.4 nm in diameter, has proven to be a superior probe label for electron microscopy (EM), giving both higher labeling density and improved access to previously hindered or restricted antigens. It may be visualized by autometallography (AMG) for use in light microscopy (LM): silver-and gold-amplified Nanogold detection has proven to be one of the most sensitive methods available for the detection of low copy number targets such as viral DNA in cells and tissue specimens. AMG enhancement has also made Nanogold an effective detection label in blots and gels. The following protocols will be described: Labeling of nuclear components in cells. Protocol for in situ hybridization and detection with fluorescein-Nanogold--or Cy3{trademark}-Nanogold-labeled streptavidin. Nanogold is an inert molecule, and generally does not interact with biological molecules unless a specific chemical reactivity is introduced into the molecule. Conjugates are prepared using site-specific chemical conjugation through reactive chemical functionalities introduced during Nanogold preparation, which allows the gold label to be attached to a specific site on the conjugate biomolecule. For example, a maleimido-Nanogold derivative, which is specific for thiol binding, is frequently attached to the hinge region of an antibody at a unique …

The National Renewable Energy Laboratory's (NREL) eighth annual Information Resources Catalog can help keep you up-to-date on the research, development, opportunities, and available technologies in energy efficiency and renewable energy. The catalog includes five main sections with entries grouped according to subject area.

Wind Power Today is an annual publication that provides an overview of the U.S. Department of Energy's Wind Energy Program accomplishments for the previous year. The purpose of Wind Power Today is to show how DOE's Wind Energy Program supports wind turbine research and deployment in hopes of furthering the advancement of wind technologies that produce clean, low-cost, reliable energy. Content objectives include: educate readers about the advantages and potential for widespread deployment of wind energy; explain the program's objectives and goals; describe the program's accomplishments in research and application; examine the barriers to widespread deployment; describe the benefits of continued research and development; facilitate technology transfer; and attract cooperative wind energy projects with industry. This 2001 edition of Wind Power Today also includes discussions about wind industry growth in 2001, how DOE is taking advantage of low wind speed regions through advancing technology, and distributed applications for small wind turbines.

Report documenting the partnership between DOEs Office of Industrial Technologies and the U.S. glass industry.

The Universal Interconnection Technology (UIT) Workshop - sponsored by the U.S. Department of Energy, Distributed Energy and Electric Reliability (DEER) Program, and Distribution and Interconnection R&D - was held July 25-26, 2002, in Chicago, Ill., to: (1) Examine the need for a modular universal interconnection technology; (2) Identify UIT functional and technical requirements; (3) Assess the feasibility of and potential roadblocks to UIT; (4) Create an action plan for UIT development. These proceedings begin with an overview of the workshop. The body of the proceedings provides a series of industry representative-prepared papers on UIT functions and features, present interconnection technology, approaches to modularization and expandability, and technical issues in UIT development as well as detailed summaries of group discussions. Presentations, a list of participants, a copy of the agenda, and contact information are provided in the appendices of this document.

School districts around the country are finding that smart energy choices can help them save money and provide healthier, more effective learning environments. By incorporating energy improvements into their construction or renovation plans, schools can significantly reduce energy consumption and costs. These savings can be redirected to educational needs such as additional teachers, instructional materials, or new computers. These design guidelines outline high performance principles for the new or retrofit design of your K-12 school. By incorporating these principles, you can create an exemplary building that is both energy and resource efficient.

The Department of Energy's Federal Energy Management Program (FEMP) established the Distributed Energy Resources (DER) Program to assist Federal agencies in implementing DER projects at their facilities. FEMP prepared this How-To Guide to assist facility managers in evaluating potential applications and benefits. It provides step-by-step advice on how to carry out a Federal DER project. It also describes and explains DER applications and potential benefits in Federal facilities; DER technologies and how to match them to applications; a step-by-step approach to implementing projects; potential barriers and how to overcome them; and resources to assist you in implementing new DER projects.

This program brochure will be handed out to the teams, sponsors, and some attendees to provide a brief overview of the competition and the fourteen entries. The brochure also outlines the sponsors reasons for participating in the Solar Decathlon. The U.S. Department of Energy is proud to sponsor the first-ever Solar Decathlon, a college and university competition that brings together our nation's brightest minds to demonstrate practical ways of producing and using energy efficiently in the home. The Solar Decathlon consists of 10 contests that encompass all the ways in which we use energy in our daily lives--from livability and comfort to daily chores and home-based work to getting around town. Sunlight is the only source of energy that can be used to generate the thermal, electrical, and mechanical power needed to compete in the 10 contests. The best looking house that can produce the most energy and use that energy the most efficiently will win. Energy efficiency and solar technologies are available for the home today, and they are affordable. At the same time, the designs of these homes are attractive and livable. The Solar Decathlon will prove that investment in renewable energy and energy-efficient technologies can reduce our …

School districts around the country are finding that the smart energy choices can help them save money and provide healthier, more effective learning environments. By incorporating energy improvements into their construction or renovation plans, schools can significantly reduce energy consumption and costs. These savings can be redirected to educational needs such as additional teachers, instructional materials, or new computers. These design guidelines outline high performance principles for the new or retrofit design of your K-12 school. By incorporating these principles, you can create and exemplary building that is both energy and resource efficient.

In Fiscal Year 2001, for the third year in a row, the solar electric market grew at more than 30%. Fueling this growth is the U.S. photovoltaic industry - the companies that design, manufacture, install, operate, and maintain all components of solar generating systems. The messages of the U.S. PV industry roadmap are taken very seriously by the U.S. Department of Energy's Office of Solar Energy Technologies. Achieving industry's goals will demand aggressive work in fundamental and exploratory research, manufacturing, and system applications to reduce the cost of solar electric systems. This is an annual report of the DOE PV Program, FY2001.

School districts around the country are finding that the smart energy choices can help them save money and provide healthier, more effective learning environments. By incorporating energy improvements into their construction or renovation plans, schools can significantly reduce energy consumption and costs. These savings can be redirected to educational needs such as additional teachers, instructional materials, or new computers. These design guidelines outline high performance principles for the new or retrofit design of your K-12 school. By incorporating these principles, you can create and exemplary building that is both energy and resource efficient.

Executive Order 13123 calls for the Federal government to conserve water as well as energy in its 500,000 facilities. To help set priorities among water-saving measures, the Federal Energy Management Program conducted a study of Federal water use in 1997. The study indicated that the government consumes more than 50% of its water in just three types of Federal facilities: housing, hospitals, and office buildings. These facilities have enough kitchens, rest rooms, and laundry areas to provide facility managers with many opportunities to begin reducing their water use (and utility costs) with appropriate water-saving fixtures and products. Therefore, this Federal Technology Alert focuses on domestic technologies, products, and appliances such as water-efficient faucets, showerheads, toilets, urinals, washing machines, and dishwashers. Conserving water also saves the energy needed to treat, pump, and heat that water in homes, businesses, and other buildings.

The North Dakota Consumer's Guide for Small Wind Electric systems provides consumers with enough information to help them determine if a small wind electric system can provide all or a portion of the energy they need for their home or business based on their wind resource, energy needs, and their economics. Topics discussed in the guide include: how to make your home more energy efficient, how to choose the right size turbine, the parts of a wind electric system, determining if there is enough wind resource on your site, choosing the best site for your turbine, connecting your system to the utility grid, and if it's possible to become independent of the utility grid using wind energy. In addition, the North Dakota guide provides state specific information that includes and state wind resource map, state incentives, and state contacts for more information.

A new high-temperature glass viscometer instrument was established and evaluated using a simulated waste glass in a comparative test with eight other laboratories and viscometers. The unit has distinct advantages in physical size, the amount of glass required for testing, and the simplicity of operation. These advantages can be important for work with radioactive materials. Results from the comparison indicate excellent accuracy and repeatability.

The trend in large-scale scientific data analysis is to exploit compute, storage and other resources located at multiple sites, and to make those resources accessible to the scientist as if they were a single, coherent system. Web technologies driven by the huge and rapidly growing electronic commerce industry provide valuable components to speed the deployment of such sophisticated systems. Jefferson Lab, where several hundred terabytes of experimental data are acquired each year, is in the process of developing a web-based distributed system for data analysis and management. The essential aspects of this system are a distributed data grid (site independent access to experiment, simulation and model data) and a distributed batch system, augmented with various supervisory and management capabilities, and integrated using Java and XML-based web services.

Excess electrons can be introduced into liquids by absorption of high energy radiation, by photoionization, or by photoinjection from metal surfaces. The electron's chemical and physical properties can then be measured, but this requires that the electrons remain free. That is, the liquid must be sufficiently free of electron attaching impurities for these studies. The drift mobility as well as other transport properties of the electron are discussed here as well as electron reactions, free-ion yields and energy levels, Ionization processes typically produce electrons with excess kinetic energy. In liquids during thermalization, where this excess energy is lost to bath molecules, the electrons travel some distance from their geminate positive ions. In general the electrons at this point are still within the coulombic field of their geminate ions and a large fraction of the electrons recombine. However, some electrons escape recombination and the yield that escapes to become free electrons and ions is termed G{sub fi}. Reported values of G{sub fi} for molecular liquids range from 0.05 to 1.1 per 100 eV of energy absorbed. The reasons for this 20-fold range of yields are discussed here.

Neutrons are an invaluable probe in a wide range of scientific, medical and commercial endeavors. Many of these applications require the recording of an image of the neutron signal, either in one-dimension or in two-dimensions. We summarize the reactions of neutrons with the most important elements that are used for their detection. A description is then given of the major techniques used in neutron imaging, with emphasis on the detection media and position readout principle. Important characteristics such as position resolution, linearity, counting rate capability and sensitivity to gamma-background are discussed. Finally, the application of a subset of these instruments in radiology and tomography is described.

This paper consists of three parts. The first part is concerned with the parameterization of cloud microphysics in climate models. We demonstrate the crucial importance of spectral dispersion of the cloud droplet size distribution in determining radiative properties of clouds (e.g., effective radius), and underline the necessity of specifying spectral dispersion in the parameterization of cloud microphysics. It is argued that the inclusion of spectral dispersion makes the issue of cloud parameterization essentially equivalent to that of the droplet size distribution function, bringing cloud parameterization to the forefront of cloud physics. The second part is concerned with theoretical investigations into the spectral shape of droplet size distributions in cloud physics. After briefly reviewing the mainstream theories (including entrainment and mixing theories, and stochastic theories), we discuss their deficiencies and the need for a paradigm shift from reductionist approaches to systems approaches. A systems theory that has recently been formulated by utilizing ideas from statistical physics and information theory is discussed, along with the major results derived from it. It is shown that the systems formalism not only easily explains many puzzles that have been frustrating the mainstream theories, but also reveals such new phenomena as scale-dependence of cloud droplet size …

The mathematical modeling of the transport and transformation of trace species in the atmosphere is one of the scientific tools currently used to assess atmospheric chemistry, air quality, and climatic conditions. From the scientific but also from the management perspectives accurate inventories of emissions of the trace species at the appropriate spatial, temporal, and species resolution are required. There are two general methodologies used to estimate regional to global emissions: bottom-up and top-down (also known as inverse modeling). Bottom-up methodologies to estimate industrial emissions are based on activity data, emission factors (amount of emissions per unit activity), and for some inventories additional parameters (such as sulfur content of fuels). Generally these emissions estimates must be given finer sectoral, spatial (usually gridded), temporal, and for some inventories species resolution. Temporal and spatial resolution are obtained via the use of surrogate information, such as population, land use, traffic counts, etc. which already exists in or can directly be converted to gridded form. Speciation factors have been and are being developed to speciate inventories of NO{sub x}, particulate matter, and hydrocarbons. Top-down (inverse modeling) methodologies directly invert air quality measurements in terms of poorly known but critical parameters to constrain the emissions needed …