On the choice of reference mutant states in the application of the double-mutant cycle method

Pairwise interactions in proteins can be detected and, in certaincircumstances, their strength measured by applying the methodof double-mutant cycles. Such cycles comprise wild type protein,two single mutants and the corresponding double mutant The analysisof double-mutant cycles is most straightforward when the mutationsare to alanine since interactions are mostly removed withoutnew interactions being formed. Here, ‘not-to-alanine’double-mutant cycles are analysed. It is shown that a ‘not-to-alanine’double-mutant cycle can be decomposed into four double-mutantcycles with mutations only to alanine. The coupling energy correspondingto the ‘not-to-alanine’ double-mutant cycle is expressedas a function of the coupling energies of these four cycles.     

Probabilistic optimal solution assessment for DCOPs

Distributed Constraint Optimization Problems (DCOPs) are widely used in Multi-Agent Systems for coordination and scheduling. The present paper proposes a heuristic algorithm that uses probabilistic assessment of the optimal solution in order to quickly find a solution that is not far from the optimal one. The heuristic assessment uses two passes by the agents to produce a high-quality solution. Extensive performance evaluation demonstrates that the solution of the proposed probabilistic assessment algorithm is indeed very close to the optimum, on smaller problems where this could be measured. In larger set-ups, the quality of the solution is demonstrated relatively to standard incomplete search algorithms.     

Conjugates of Unsaturated Fatty Acids with Propylene Glycol as Potentially Less-Irritant Skin Penetration Enhancers

Fatty acids (FA) are well known as efficient enhancers for transdermal delivery of drugs; however, their frequent dermal toxicity limits their regular use. In order to utilize the fatty acid as a safe enhancer devoid of its irritant effect, we have synthesized and evaluated a series of fatty acids conjugated to propylene glycol (FA-PG). Each one of the conjugates was prepared as a mono- or di- acyl ester derivative. The effects of the synthetic enhancers on the porcine skin permeability were evaluated in a diffusion cell system using lidocaine as the model drug. In addition, in vivo examinations in rabbits were preformed for skin toxicological evaluation. The results indicate that among the FA-PG conjugates, oleic acid (C18:1_n–9)-PG, linoleic acid (C18:2_n–6)-PG and α-linolenic acid (C18:3_n–3)-PG, mono- or di-esters, enhance the penetration of lidocaine relatively to the vehicle (without enhancer). The conjugates of oleic acid (C18:1_n–9) and linoleic acid (C18:2_n–6) with PG have demonstrated a similar enhancing effect as the corresponding free fatty acids. Interestingly, although the mono- or the di- conjugates of α-linolenic acid (C18:3_n–3) with PG enhanced the lidocaine flux as the other two fatty acid conjugates, they resulted in a reduced permeability as compared to the action of their free acid. In addition, the mono-conjugates of α-linolenic acid (C18:3_n–3) with PG exhibited elevated skin irritation in rabbits (relative to the fatty acid alone) compared to the significantly reduced irritation of oleate-PG and linoeate-PG mono-conjugates. In conclusion, except saturated FA-PG and α-linolenic acid (C18:3_n–3)—PG mono-conjugates, unsaturated fatty acids (e.g., oleic and linoleic acids) after conjugation to PG may be safe and effective enhancers for delivering topical drugs.     

Organic Fluorine Compounds. Part XXXVII the Preparation of ω-Amino-α-Fluroacids

γ-Amino-α-fluorobutyric acid (V) and ?-amino-α-fluorocaproic acid (VII) have been prepared from the corresponding phthalimido-α-bromo-acid anilides (or other amides) through reaction with potassium fluoride and subsequent hydrolysis.     

Optimization of the Abencor system to extract olive oil from irrigated orchards

Studying the composition of olive oil requires cold‐press olive oil extraction. One of the most common laboratorial mills is the Abencor system. However, its operation protocol was formulated decades ago for Spanish olive varieties from traditionally rain‐fed orchards. We modified this protocol for use with “Barnea” and “Picual” olives from irrigated orchards that are characterized by high water content. Independent effects of malaxation time, temperature, water addition and talc addition on extraction efficiency, and major quality indices of virgin olive oil were studied. Overall, addition of talc to the fruit paste was the most significant treatment in terms of yield and quality of the oil although its effect was cultivar dependent. Improved oil yield was particularly significant for “Picual.” Extended malaxation time was also effective in improving oil extractability. Addition of talc generally improved oil‐quality parameters, while water addition had the opposite effect. Yet, quality parameters remained within the extra virgin level. Temperature increments reduced oil quality. The need to adapt a modified protocol for use with fruits from irrigated orchards that will facilitate critical comparison of results obtained from different agronomic theses and different laboratories is highlighted. It is recommended that each laboratory develops an appropriate protocol for the operation of the Abencor system in accordance to the characteristics of the olive fruit they are working with. Practical applications: Abencor system serves as the major laboratorial mill world‐wide. Those mills allow the researchers to characterize olive oil in accordance to the treatments received by the trees. This cannot be done in commercial mills. The system operation protocol was established decades ago for fruits from rain‐fed orchards. In the past decade there was a rapid increase in the use of irrigation in olive orchards and therefore it is crucial to optimize the operation protocol for fruit with relatively high water content. In the current work we have evaluated the influence of a series of technological parameters (i.e., talc and water addition, malaxation time, and temperature) on the extraction efficiency and quality indices of olive oil. This allowed us to present a modified protocol for the Abencor system operation suitable for olive fruit of irrigated orchards that will facilitate a reliable representation of the influence of different treatments on the yield and characteristics of the olive oil.     

Bond over direct support of deformed rebars in normal and high strength concrete with and without fibers

This paper describes results of the second stage of a research on the bonding of deformed bars in normal and high strength concrete with and without fibers. The current study focused on the effect of confinement conditions, which are present over a direct support of a reinforced concrete beam, and compares these results with data obtained in the first stage of the research. The experimental work consisted of pullout tests, which were based on the standard RILEM flexural bond test (??beam test??) of deformed steel bars with diameters of 12 and 20?mm. Results revealed an increase in the normalized bond strength due to support conditions. An unstable post-peak slip of the tested rebar was observed when located over the support, whereas bars bonded near mid-span exhibited controlled bond?Cslip throughout the test. Up to peak load, however, bond?Cslip relations exhibited higher energy absorption over the support than near mid-span. Inclusion of fibers had only a minor effect on bond strength but had a significant influence on pre-peak energy absorption. A previously developed model of bond strength shows good agreement with current results when applying an increase factor due to the support effect.     

Cell-free protein synthesis and assembly on a biochip

Biologically active complexes such as ribosomes and bacteriophages are formed through the self-assembly of proteins and nucleic acids. Recapitulating these biological self-assembly processes in a cell-free environment offers a way to develop synthetic biodevices. To visualize and understand the assembly process, a platform is required that enables simultaneous synthesis, assembly and imaging at the nanoscale. Here, we show that a silicon dioxide grid, used to support samples in transmission electron microscopy, can be modified into a biochip to combine in situ protein synthesis, assembly and imaging. Light is used to pattern the biochip surface with genes that encode specific proteins, and antibody traps that bind and assemble the nascent proteins. Using transmission electron microscopy imaging we show that protein nanotubes synthesized on the biochip surface in the presence of antibody traps efficiently assembled on these traps, but pre-assembled nanotubes were not effectively captured. Moreover, synthesis of green fluorescent protein from its immobilized gene generated a gradient of captured proteins decreasing in concentration away from the gene source. This biochip could be used to create spatial patterns of proteins assembled on surfaces.     

Regional Concentration and Dynamics of Fast-growing Industries in Baden-Württemberg and Israel

Fast-growing industries are regarded as providing an above-average contribution to production, employment and innovation. Due to necessary knowledge spillovers and a high product innovation rate, these industries are expected to have a locational bias towards central, metropolitan regions guaranteeing a risk- and uncertainty-minimizing industrial atmosphere. Using statistical data on the regional distribution and composition of fast-growing industrial branches in Baden-Württemberg and Israel, it is the objective of this paper to analyse the spatial distribution process of fast-growing industries and to answer the question if also non-metropolitan regions provide favourable location conditions which could be made the starting point for innovation-oriented regional development strategies. Based on different methods of regional analysis, like concentration indices and shift-share analysis, our results indicate that although the highest share of fast-growing industrial branches can still be found in central regions, spatial dispersion towards intermediate and peripheral regions occurred between the late 1980s and early 1990s in Israel as well as in Baden-Württemberg. This decentralization process makes it clear that these industries can be an important target group for disparity-reducing regional policy.     

Hybrid concentrated photovoltaic and thermal power conversion at different spectral bands

The option to use the beam down optics of a solar tower system for large-scale and grid-connected concentrated photovoltaic (PV) cells is examined. The rationale is to use this system to split the solar spectrum. Part of the spectrum can be utilized for PV cells. For instance, but not limited to, mono-crystalline silicon cells can convert the 600–900 nm band to electricity at an efficiency of 55–60%. The rest of the spectrum remains concentrated and it can be used thermally to generate electricity in Rankine–Brayton cycles or to operate chemical processes. Two optical approaches for a large-scale system are described and analyzed. In the first concept, the hyperboloid-shaped tower reflector is used as the spectrum splitter. Its mirrors can be made of transparent fused silica glass, coated with a dielectric layer, functioning as a band-pass filter. The transmitted band reaches the upper focal zone, where an array of PV modules is placed. The location of these modules and their interconnections depend on the desirable concentration level and the uniformity of the flux distribution. The reflected band is directed to the second focal zone near the ground, where a compound parabolic concentrator is required to recover and enhance the concentration to a level depending on the operating temperature at this target. In the second approach, the total solar spectrum is reflected down by the tower reflector. Before reaching the lower focal plane, the spectrum is split and filtered. One band can be reflected and directed horizontally to a PV array and, in this case, the rest of the spectrum is transmitted to the lower focal plane. To illustrate the feasibility of these options, commercial silicon cells with antireflective coating, intended to operate under concentrated solar radiation in the range of 200–800 suns, were chosen. The results show that 6.5 MWe from the PV array and 11.1 MWe from a combined cycle can be generated starting from a solar heat input of 55.6 MW.     

Expectations of Grassroots Community Leadership in Times of Normality and Crisis

The article compares the preferences of community members for the transformational and transactional leadership styles of grassroots leaders at times of normality with those during a crisis. A structured questionnaire was administered to members of a community that experienced security crises on the Lebanese border of Israel before the 2006 Lebanon War. It reveals differences in the dominance of preferred leadership styles depending on the type of situation – normality or crisis. The article discusses these differences, compares the findings with those of other studies and considers their practical implications.