Engineering of protein epitopes: a single deletion in a snake toxin generates full binding capacity to a previously unrecognized antibody

Structural features associated with the ability of a monoclonalantibody (mAb) to discriminate between protein variants areidentified and engineered. The variants are the curaremimetictoxin from Naja nigricollis and erabutoxin a or b from Laticaudasemifasciata which differ from each other by 16 substitutionsand one insertion. The neutralizing mAb M1 recognizes with highaffinity a topographical epitope on the surface of toxin , butfails to recognize the erabutoxins although they possess mostof the residues forming the presumed epitope. Examinations ofthe toxin and erabutoxin 3-D structures and molecular dynamicssimulations reveal several differences between the variants.In particular, the region involving the ß-turn 17–24is organized differently. Analysis of the differences foundin this region suggests that the insertion (or deletion) atposition 18 of the variant amino add sequences is particularlyimportant in determining the differential cross-reactivity.To test this proposal, residue 18 was deleted in one erabutoxinusing sitedirected mutagenesis, and the biological propertiesof the resulting mutant were examined. We found that full antigenicitywas restored in the previously unrecognized variant. The implicationsof this finding are discussed.     

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes

Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the pro‐fibrogenic effects of a library of MWCNTs in vitro and in vivo are chosen. Ex vivo analysis of IL‐1β production in bone marrow‐derived macrophages (BMDMs) as molecular initiating event (MIE) is performed. The order of cytokine production (Balb/c > A/J > C57Bl/6 > NOD/ShiLtJ) in BMDMs is also duplicated during assessment of IL‐1β production in the bronchoalveolar lavage fluid of the same mouse strains 40 h after oropharyngeal instillation of a representative MWCNT. Animal test after 21 d also confirms a similar hierarchy in TGF‐β1 production and collagen deposition in the lung. Statistical analysis confirms a correlation between IL‐1β production in BMDM and the lung fibrosis. All considered, these data demonstrate that genetic background indeed plays a major role in determining the pro‐fibrogenic response to MWCNTs in the lung.     

Lateral Magnetically Modulated Multilayers by Combining Ion Implantation and Lithography

The combination of lithography and ion implantation is demonstrated to be a suitable method to prepare lateral multilayers. A laterally, compositionally, and magnetically modulated microscale pattern consisting of alternating Co (1.6 µm wide) and Co‐CoO (2.4 µm wide) lines has been obtained by oxygen ion implantation into a lithographically masked Au‐sandwiched Co thin film. Magnetoresistance along the lines (i.e., current and applied magnetic field are parallel to the lines) reveals an effective positive giant magnetoresistance (GMR) behavior at room temperature. Conversely, anisotropic magnetoresistance and GMR contributions are distinguished at low temperature (i.e., 10 K) since the O‐implanted areas become exchange coupled. This planar GMR is principally ascribed to the spatial modulation of coercivity in a spring‐magnet‐type configuration, which results in 180° Néel extrinsic domain walls at the Co/Co‐CoO interfaces. The versatility, in terms of pattern size, morphology, and composition adjustment, of this method offers a unique route to fabricate planar systems for, among others, spintronic research and applications.     

Heavy metal removal from simulated wastewater using electrochemical technology: optimization of copper electrodeposition in a membraneless fluidized bed electrode

Heavy metal removal from industrial wastewaters has been intensively studied, since it is well known that they can cause severe problems to human health and aquatic life, even at very low concentrations. In this work, it was demonstrated that electrodeposition in fluidized bed electrode (FBE) can be efficiently employed to remove metal ions from solution, avoid contamination, and recover the metal. Copper electrodeposition from diluted solutions was efficiently performed using a membraneless FBE. The average current efficiency (ACE), average energy consumption (AEC), and space–time yield (AY) was optimized taking into account the operational and process variables. It was noted that for all response variables studied, the raise of supporting electrolyte concentration (C _s) contributed to improvements in the process. The operational conditions current (I) and bed expansion (E) determined the values of CE, Y, and EC under activated control, but the initial copper concentration (C ₀) determined how long the electrodeposition process will work under activated or mass transfer control, thus affecting the average values of CE, Y, and EC. Considering C ₀ of 500 mg L^?1, copper can be optimally recovered with ACE >60 %, AY >38 kg h^?1 m^?3, and AEC <4.0 kWh kg^?1 by applying the lowest I and the highest levels of E and C _s. It was concluded that the electrochemical technology using a membraneless FBE reactor is economically competitive and be applied for the treatment of wastewaters contaminated with copper or other metals.     

Minimum Setup Minimum Aberration Two‐level Split‐plot Type Designs for Physical Prototype Testing

Although new technologies allow for less effort in prototyping, physical testing still remains an important step in the product development cycle. Well‐planned experiments are useful to guide the decision‐making process. During the design of an experiment, one of the challenges is to balance limited resources and system constraints to obtain useful information. It is common that prototypes are composed of several parts, with some parts more difficult to assemble than others. And, usually, there is only one piece available of each part type and a large number of different setups. Under these conditions, designs with randomization restrictions become attractive approaches. Considering this scenario, a new and additional criterion, minimum setup, to construct split‐plot type designs is presented. Designs with the minimum number of setups of the more difficult parts, which are especially useful for screening purposes in physical prototype testing, are discussed. The use of the proposed criterion combined with minimum aberration for selecting a regular design is shown through a real application in testing car prototypes. As a tool to practitioners, catalogs of selected 32‐run minimum setup minimum aberration split‐split‐plot and split‐split‐split‐plot designs are presented. More complete catalogs are available as Supporting information. Copyright © 2015 John Wiley & Sons, Ltd.     

Investigation of Ablation Efficiency of Stainless Steel Using Pulsed Lasers in Burst Mode

Due to its high corrosion resistance and mechanical properties, stainless steel is commonly used in various industrial applications. Although different types of stainless steel are similar in their chemical composition, they can differ significantly in their thermal diffusivity. This property is relevant in the ability of a material to conduct heat and thus, in laser processing. In this frame, this study compares the ablation efficiency and characteristics of polished stainless steel samples of the alloys AISI 304, AISI 420, and AISI 316Ti. They are irradiated with single ultrashort pulses having pulse durations between 250 fs and 10 ps as well as using GHz burst modii. The goal is to investigate the differences in both the ablation threshold and the ablation rate to improve the ablation efficiency. The results show that shorter pulse durations lead to a more efficient ablation process. On the other hand, GHz bursts are found to be, in general, less efficient. In addition, there is a significant difference in the surface morphology depending on the process parameters. The differences in the thermal diffusivity do not significantly influence the ablation threshold fluence but surface morphology and the ablation rate.     

Infrastructure Federation Through Virtualized Delegation of Resources and Services

Infrastructure federation is becoming an increasingly important issue for modern Distributed Computing Infrastructures (DCIs): Dynamic elasticity of quasi-static Grid environments, incorporation of special-purpose resources into commoditized Cloud infrastructures, cross-community collaboration for increasingly diverging areas of modern e-Science, and Cloud Bursting pose major challenges on the technical level for many resource and middleware providers. Especially with respect to increasing costs of operating data centers, the intelligent yet automated and secure sharing of resources is a key factor for success. With the D-Grid Scheduler Interoperability (DGSI) project within the German D-Grid Initiative, we provide a strategic technology for the automatically negotiated, SLA-secured, dynamically provisioned federation of resources and services for Grid-and Cloud-type infrastructures. This goal is achieved by complementing current DCI schedulers with the ability to federate infrastructure for the temporary leasing of resources and rechanneling of workloads. In this work, we describe the overall architecture and SLA-secured negotiation protocols within DGSI and depict an advanced mechanism for resource delegation through means of dynamically provisioned, virtualized middleware. Through this methodology, we provide the technological foundation for intelligent capacity planning and workload management in a cross-infrastructure fashion.     

Post-processing and visualization techniques in 2D boundary element analysis

Most post-processors for boundary element (BE) analysis use an auxiliary domain mesh to display domain results, working against the profitable modelling process of a pure boundary discretization. This paper introduces a novel visualization technique which preserves the basic properties of the boundary element methods. The proposed algorithm does not require any domain discretization and is based on the direct and automatic identification of isolines. Another critical aspect of the visualization of domain results in BE analysis is the effort required to evaluate results in interior points. In order to tackle this issue, the present article also provides a comparison between the performance of two different BE formulations (conventional and hybrid). In addition, this paper presents an overview of the most common post-processing and visualization techniques in BE analysis, such as the classical algorithms of scan line and the interpolation over a domain discretization. The results presented herein show that the proposed algorithm offers a very high performance compared with other visualization procedures.