Simultaneous Use of in Silico Design and a Correlated Mutation Network as a Tool To Efficiently Guide Enzyme Engineering

In order to improve the efficiency of directed evolution experiments, in silico multiple‐substrate clustering was combined with an analysis of the variability of natural enzymes within a protein superfamily. This was applied to a Pseudomonas fluorescens esterase (PFE I) targeting the enantioselective hydrolysis of 3‐phenylbutyric acid esters. Data reported in the literature for nine substrates were used for the clustering meta‐analysis of the docking conformations in wild‐type PFE I, and this highlighted a tryptophan residue (W28) as an interesting target. Exploration of the most frequently, naturally occurring amino acids at this position suggested that the reduced flexibility observed in the case of the W28F variant leads to enhancement of the enantioselectivity. This mutant was subsequently combined with mutations identified in a library based on analysis of a correlated mutation network. By interrogation of <80 variants a mutant with 15‐fold improved enantioselectivity was found.     

Application Scenarios in Streaming-Oriented Embedded-System Design

A design method for handling increasingly dynamic real-time embedded-system applications can help developers cope with stringent system and market requirements. This method groups an application's operation modes into application scenarios and describes how to incorporate them in the overall design process. An automated scenario-based design trajectory reduces the energy consumption of a streaming application running on a single processor platform via dynamic voltage and frequency scaling.     

National orientation of Ukrainian journals: means-ends decoupling in a semi-peripheral state

Scientometrics - Employing an institutionalist perspective, this article aims to explore the implementation of the global model of the international journal in Ukraine. Focusing on selected...     

Recent advances and future challenges in the use of nanoparticles for the dispersal of infectious biofilms

Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious biofilms.Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation.We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy.Deoxyribonuclease(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal.Also,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as dispersants.On their own,dispersants do not inhibit bacterial growth or kill bacterial pathogens.Both natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like pH-responsive micelles,liposomes or hydrogels.Depending on their composition,nanoparticles can also possess intrinsic dispersant properties.Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells.However,this sudden increase in bacte-rial concentration can also cause sepsis.Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat.Importantly,biofilm remaining after dispersant administration appears more susceptible to existing antibiotics.Being part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been observed.Dispersants are therewith promising for the control of infectious biofilms.     

Photovoltaics in an architectural context

In well‐populated areas, such as western Europe, PV is often integrated into the building envelope. Despite the fact that there are many examples showing that PV can be an aesthetically neutral or visually attractive element in architecture, many BIPV systems display few architectural qualities. But if well applied, PV can increase a building's character and value. Within Task 7 of the IEA PVPS programme a team of experts with an architectural background studied which key requirements needed to be complied with (design criteria for good‐quality PV projects) in order to produce successful PV integration. These criteria are discussed in the article. PV is not automatically considered an indispensable material in architectural terms. This is why, no matter how well it is integrated, PV remains an ‘added’ element. Architects can take this as their starting point and can use one of the design approaches that are presented in the article. These criteria for incorporating PV in the building design and the design criteria for good‐quality PV projects are important to architects and architectural critics in determining why a BIPV project, be it their own design or that of a colleague, is or is not aesthetically pleasing. This offers learning opportunities and reasons for follow‐up or improvement options. Architects who apply PV in a well‐thought‐out way can make their clients very happy, and thereby contribute to a greater acceptance of PV technology. Copyright © 2004 John Wiley & Sons, Ltd.     

Rheological behavior and thermomechanical properties of polyethylene—Glycidyl methacrylate vitrimers utilizing disulfide exchange

Four vitrimers were made using polyethylene – glycidyl methacrylate copolymer (PE-GMA) and 3,3′ – dithiodipropionic acid (DTDPA) using a two-step procedure. The amount of DTDPA added was varied, and therefore, the crosslink density was also varied. Rheological experiments were performed. The vitrimers exhibit different rheological behavior depending on the angular frequency applied, which most likely stems from the presence of a crosslinked network. Additionally, there appears to be an on-going reaction occurring during rheological tests, all of which occur above the melting temperature. Thermal and mechanical tests were also conducted. Thermomechanical testing determined that increasing crosslink density resulted in a decrease in the yield strength.     

A toolkit for parallel functional programming

Our toolkit for the design and implementation of parallel functional programs supports the stepwise development of parallel programs from a high level sequential specification to an optimised parallel implementation. The toolkit is used as follows:

• 1 The algorithm to be implemented is specified in a functional language. The program is debugged and tested using an interpreter.
• 2 The program is compiled for a sequential machine. Its performance is analysed and improved.
• 3 Annotation-driven transformations are applied to the program to indicate parallel tasks. Simulations at task level, basic block level and bus transaction level make it possible to analyse the parallel performance of the program at three levels of detail.
• 4 When the performance is optimised using the simulators, the program is executed on a genuine parallel machine.

Several programs have been developed with the toolkit. A program that simulates tidal flow in an estuary of the North sea is presented as a case study to demonstrate the merits of the toolkit when developing complex parallel programs. The toolkit not only supports the design of parallel applications, it also allows the study of important concepts in parallel computer architecture. These include the behaviour of cached memory systems, bus protocols, scheduling algorithms and memory management algorithms.     

Self-Targeted Co-Delivery of an Antibiotic and a Cancer-Chemotherapeutic from Synthetic Liposomes for the Treatment of Infected Tumors

Intra-tumor bacteria promote tumor growth and inactivate cancer-chemotherapeutics, causing poor treatment prognoses. Combined administration of cancer-chemotherapeutics and antibiotics may disturb the oral and intestinal microflora in critically-ill patients. To establish intra-tumor co-delivery of cancer-chemotherapeutics and antibiotics, gemcitabine and ciprofloxacin are loaded in so-called “self-targeting”, highly blood-compatible, synthetic DCPA-H₂O liposomes equipped with complexed water for pH-responsiveness. Liposomal pH-responsiveness can be maintained by in-shell loading of gemcitabine and in-core loading of ciprofloxacin. These dual-loaded liposomes are stealthily transported in the blood circulation to accumulate in the acidic environment of an infected tumor. Upon tumor self-targeting, liposomes are fused with tumor cells and infecting bacteria and are disassembled to simultaneously release gemcitabine and ciprofloxacin. Treatment of mice with these self-targeting liposomes yields significantly higher responses of Escherichia coli infected tumors with respect to both infection and tumor volume than gemcitabine and ciprofloxacin co-delivered from non-self-targeting liposomes or free gemcitabine with or without ciprofloxacin in solution.