Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Contractor Prebid Planning Principles

Planning is an essential function of project management. Yet, many small- and medium-sized contractors do a relatively poor job of operational planning. Better prebid plans will reduce costs, shorten schedules, and improve labor productivity. Unfortunately, the published literature offers little guidance for smaller contractors on what constitutes effective planning. Most papers describe planning as a macrolevel process for owners. Most emphasize scope definition for industrial projects. This paper describes a microlevel planning process for contractors. It consists of eight steps which are: (1) assess contract risks; (2) develop a preliminary execution plan; (3) develop site layout plans; (4) identify the sequences that are essential-to-success; (5) develop detailed operational plans; (6) develop proactive strategies to assure construction input into design; (7) revise the preliminary plan; and (8) communicate and enforce the plan. The entire process is illustrated with a case study project and is fully illustrated with figures which show how to integrate the work of multiple contractors, keep key resources (crews or equipment) fully engaged with no downtime, provide time buffers so the work of follow on crews can be efficiently done, expedite the schedule using multiple work stations and concurrent work, ways to communicate the work plan to the superintendent and foremen, and how to assess the feasibility of various work methods. The steps are easy to understand and implement. They will yield immediate positive results.     

History of Construction, Engineering, and Management in the Department of Civil and Environmental Engineering at Penn State

At Penn State, the credit for broadening the Civil Engineering Department’s longstanding academic focus on analysis and design to include the construction phase must go to Dr. Harmer A. Weeden and his longtime associate Dr. Thomas D. Larson. Jack H. Willenbrock joined the Department as an Instructor in June 1968 and grew the construction program so that today about a fourth to a third of the civil undergraduates obtain employment in the construction industry. The program has awarded about 250 postbaccalaureate degrees.     

MODE-type algorithm for estimating damped, undamped, or explosive modes

We propose a new algorithm for estimating the parameters of damped, undamped, or explosive sinusoidal signals. The algorithm resembles the MODE algorithm, which is commonly used for direction of arrival estimation in the array signal processing field. It is derived as a natural approximation to an asymptotically (high-SNR) optimal parameter estimator and has excellent statistical accuracy. Nevertheless, it is computationally simple and easy to implement. Numerical examples are included to illustrate the performance of the proposed method.This work has been supported by the Swedish Research Council for Engineering Sciences (TFR).     

Seasonal variation in the role of grey squirrels as hosts of Ixodes ricinus, the tick vector of the Lyme disease spirochaete, in a British woodland

The partition of free fatty acids (FFA) to egg-phosphatidylcholine (egg-PC) and egg-phosphatidylethanolamine (egg-PE) vesicles was studied. Upon the addition of FFA to the suspension of vesicles, the pH of the aqueous phase changed depending on the length and saturation of the FFA hydrocarbon chain, as well as on the vesicle composition. The medium pH decreased faster if FFA was added to egg-PE as compared to egg-PC vesicles. The fluorescent free fatty acid indicator (ADIFAB) was used to measure the amount of FFA remaining in the aqueous phase. Most of the FFA added to the suspension of egg-PE vesicles remained in the aqueous phase, whereas in the presence of egg-PC vesicles the FFA partitioned preferentially into the lipid phase. The amount of FFA incorporated into the lipid bilayers was estimated by measuring the changes of pH at the lipid bilayer surface, using fluorescein-PE. At high surface concentrations of FFA, decreasing pH at the bilayer surface caused the protonation of FFA, and raised the pK of FFA at the bilayer surface from 5 to about 7. The partition of FFA in egg-PE vesicles was an order of magnitude lower than that in egg-PC vesicles. The incorporation amount was determined more by the molecular packing than by the nature of lipid headgroups, because steroylcaprioyl-PE, which preferred the bilayer structure, behaved more like egg-PC than egg-PE. Understanding FFA partition characteristics would help to interpret the hydrolysis measurements of phospholipids, and to explain many biological activities of FFA.     

Large-scale quantum mechanical simulations of high- Z metals

High-Z metals constitute a particular challenge for large-scale ab initio electronic-structure calculations, as they require high resolution due to the presence of strongly localized states and require many eigenstates to be computed due to the large number of electrons and need to accurately resolve the Fermi surface. Here, we report recent findings on high-Z metals, using an efficient massively parallel planewave implementation on some of the largest computational architectures currently available. We discuss the particular architectures employed and methodological advances required to harness them effectively. We present a pair-correlation function for U, calculated using quantum molecular dynamics, and discuss relaxations of Pu atoms in the vicinity of defects in aged and alloyed Pu. We find that the self-irradiation associated with aging has a negligible effect on the compressibility of Pu relative to other factors such as alloying. The US Goverment’s right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged.     

The effect of flaming on computer-mediated negotiations

There is an increasing use of computer media for negotiations. However, the use of computer-mediated channels increases the hostile expressions of emotion, termed flaming. Although researchers agree that flaming has important effects on negotiation, predictions concerning these effects are inconsistent, suggesting a need for further investigation. We address this need by extending current flaming and negotiation research in two ways. First, we identify two different types of flaming: that which is motivated by perceptions concerning the negotiating opponent (e.g., he/she is unfair) and that which is motivated by perceptions concerning the negotiating context (e.g., the communication channel is too slow). Second, we differentiate between the effects of flaming on the concession behaviors of the flame sender and the flame recipient, and the effects of these behaviors on negotiated agreement. Via a laboratory study, we demonstrate that flames directed at the negotiation opponent slightly decrease the likelihood of reaching an agreement, and when an agreement is reached, it result in outcomes significantly favoring the flame recipient rather than the flame sender. In contrast, flames directed at the negotiation context significantly increase the likelihood of agreement, although outcomes still favor the flame recipient over the flame sender. These results suggest that flame senders are generally worse off than flame recipients, which provides an important basis for the strategic use of flaming in negotiations.     

Role of Inventory Buffers in Construction Labor Performance

Buffers of material stockpile (inventory) are formed at the work level in construction to help manage production. The size of material stockpiles often has an important bearing on construction project performance. In construction projects, where conditions are often uncertain and variable, some have suggested that buffers be sized and located according to the conditions. New management thinking like lean construction and theory of constraints suggests that the size of buffers needs to be managed carefully, because when oversized, buffers are wasteful, impede workflow, and hinder performance. Research has shown that project variability can be affected with the careful deployment of buffers but has not really evaluated the impact on construction labor performance. This paper reports an exploratory analysis of the relationship between inventory (buffers) and construction labor performance with data collected from three commercial projects in Brazil. In this study, the size of the buffer between rebar fabrication and installation in the construction of a structural system is compared to the labor performance of the fabrication and installation crews. The results show that some buffer helps achieve the best labor performance in the construction operations studied.     

Two-point higher-order BVPs with singularities in phase variables

The existence of solutions for singular higher-order differential equations with the Lidstone or the (n,p) boundary conditions is proved. The right-hand sides of differential equations can have singularities in the zero value of their phase variables and so higher derivatives of solutions changing their signs can pass through these singularities. Proofs are based on the method of a priori estimates, the degree theory arguments and on Vitali's convergence theorem.