Enhanced in vivo Optical Imaging of the Inflammatory Response to Acute Liver Injury in C57BL/6 Mice Using a Highly Bright Near-Infrared BODIPY Dye

Delving deeper is possible in whole-body in vivo imaging using a super-bright membrane-targeting BODIPY dye ( BD ). The dye was used to monitor homing of ex vivo fluorescently labelled neutrophils to an injured liver of dark-pigmented C57BL/6 mice. In vivo imaging system (IVIS) data conclusively showed an enhanced signal intensity and a higher signal-to-noise ratio in mice receiving neutrophils labelled with the BD dye relative to those labelled with a gold standard dye at 2 h post in vivo administration of fluorescently labelled cells. Fluorescence-activated cell sorting (FACS) confirmed that BD is nontoxic, and an exceptional cell labelling dye that opens up precision deep-organ in vivo imaging of inflammation in mice routinely used for biomedical research. The origin of enhanced performance is identified with the molecular structure and the distinct localisation of the dye within cells that enable remarkable changes in its optical parameters.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.     

法式甜品中的悠然古风

正悦舍食单的甜品从构思、制作,到最终成型起名,每一处细节都透露出店主的用心,选用中式食材制作的法甜,品尝时能从心底感受到属于东方的独特气质。莫愁在酒酿中融入淡奶,香甜醇美,马蹄增加脆口感,含在口中细细品味,就像一位古风女子婷婷袅袅地走来,温婉而有韵味。     

Conversing across cultures: East-West communication styles in work and nonwork contexts.

Four experiments provided evidence that East-West differences in attention to indirect meaning are more pronounced in work settings compared with nonwork settings as suggested by prior research on Protestant relational ideology. Study 1 compared errors in interpreting indirect messages in work and nonwork contexts across three cultures. Studies 2 and 3 examined differences in self-reported indirectness with coworkers versus nonwork acquaintances across three cultures controlling for variation in individualism- collectivism. Study 4 examined self-reported indirectness in bicultural managers, and experimentally manipulated the salience of Western versus Eastern culture. The results showed that Americans, but not East Asians, were less attentive to indirect cues in work than nonwork settings and that East-West differences in indirectness were greater in work than nonwork settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A workbook-based methodology for implementing concurrent engineering

Concurrent Engineering demands a new way of working and many organisations experience difficulty during implementation. The research described in this paper has the aim to develop a paper-based workbook style methodology that companies can use to increase the benefits generated by Concurrent Engineering, while reducing implementation costs, risk and time.

The three-stage methodology provides guidance based on knowledge accumulated from implementation experience and best practitioners. It encourages companies to learn to manage their Concurrent Engineering implementation by taking actions which expose them to new and valuable experiences. This helps to continuously improve understanding of how to maximise the benefits from Concurrent Engineering.

The methodology is particularly designed to cater for organisational and contextual uniqueness, as Concurrent Engineering implementations will vary from company to company. Using key actions which improve the Concurrent Engineering implementation process, individual companies can develop their own ‘best practice’ for product development. The methodology ensures that key implementation issues, which are primarily human and organisational, are addressed using simple but proven techniques.

This paper describes the key issues that the majority of companies face when implementing Concurrent Engineering. The structure of the methodology is described to show how the issues are addressed and resolved. The key actions used to improve the Concurrent Engineering implementation process are explained and their inclusion in the implementation methodology described.

Relevance to industry

Implementation of Concurrent Engineering concepts in manufacturing industry has not been a straightforward process. This paper describes a workbook-style tool that manufacturing companies can use to accelerate and improve their Concurrent Engineering implementation.     

Neighbours or Enemies? Competing Variants Causing Differences in Transitional Dialects

The aim of this study is to show how clusteranalysis can shed light on very complexvariation in a transitional dialect zone ineastern Finland. In the course of history thisarea has been on the border between Sweden andRussia and the population has clearly been oftwo kinds: the Savo people and the Karelians.It is a well-known fact that there is variationamong these dialects, but the spread and extentof the variation has not been demonstrated previously.The idiolects of the area were studied in thelight of ten phonological and morphologicalfeatures. The material consisted of recordingsof 198 idiolects, totalling around 195 hoursand representing 19 parishes. The variation wasanalysed using hierarchical cluster analysis.While the analysis showed the extent of thevariation between idiolects and parishes, italso demonstrated how the effects of the oldparishes, borders and settlements are stillvisible in the dialects. On the parish level,the data formed clear clusters that correspondwith the main dialects in the area and itssurroundings. On the idiolect level, however,the speakers from the surrounding areas formedfairly homogenous clusters but the idiolectsfrom the Savonlinna area were spread acrossalmost all clusters.     

Refactoring in Maintenance and Development of Z Specifications and Proofs

Once you have proved your refinement correct, that is not the end. Real products, and their accompanying specifications, develop over time, with new improved versions having added functionality. There are new maintenance issues that arise when altering and upgrading pre-existing large specifications and their respective proofs.We show how concepts from refactoring can be used to structure this process, and provide a means for well-defined, disciplined modifications. Additionally, we discuss how the analogy between proof and refactoring, as meaning preserving transforms, can be used to suggest the development of a refactoring toolset, and thence a refinement toolset.     

Virtualizing the real: a virtual reality contemporary sculpture park for children

This paper discusses a virtual reality experience for a contemporary sculpture park, Jupiter Artland, developed in Minecraft targeting 9–11-year-old children. Issues of fidelity, realism and authenticity are considered, examining the use of Minecraft to create visual representations loosely coupled with reality that generate affective responses. We discuss the build of our virtual sculpture park outlining our approach to creating a facsimile of the sculpture park through adopting practices from the Minecraft community and refining and improving the artworks and experience informed by a class of 9–10 year old children. Using the real and virtual sculpture parks we explore the impact of engaging with the real before the virtual Jupiter Artland and vice versa, with the results from a three class study outlined in this paper.