In vitro and in vivo investigations of upconversion and NIR emitting Gd2O3:Er3+,Yb3+ nanostructures for biomedical applications

The use of an “over 1000-nm near-infrared (NIR) in vivo fluorescence bioimaging” system based on lanthanide containing inorganic nanostructures emitting in the visible and NIR range under 980-nm excitation is proposed. It may overcome problems of currently used biomarkers including color fading, phototoxicity and scattering. Gd₂O₃:Er³⁺,Yb³⁺ nanoparticles and nanorods showing upconversion and NIR emission are synthesized and their cytotoxic behavior is investigated by incubation with B-cell hybridomas and macrophages. Surface modification with PEG-b-PAAc provides the necessary chemical durability reducing the release of toxic Gd³⁺ ions. NIR fluorescence microscopy is used to investigate the suitability of the nanostructures as NIR–NIR biomarkers. The in vitro uptake of bare and modified nanostructures by macrophages is investigated by confocal laser scanning microscopy. In vivo investigations revealed nanostructures in liver, lung, kidneys and spleen a few hours after injection into mice, while most of the nanostructures have been removed from the body after 24?h.     

MARC事务所：适应,更新和转变

在人们日益忧虑资源浪费、环境衰退和污染的时代,建筑师们被鼓励考虑如何以最小程度千预和充分利用材料的方式创造性地满足客户的需求——无论是新建的项目,还是改造更新的项目,都同样如此.建筑业是最大的单一污染源之一,其污染不仅包含对不可替代资源的开发,也包括建设过程中产生的悬浮颗粒、废水和固体污染物.来自重型机器和卡车的柴油机颗粒、建筑中使用的标准高毒性材料——涂料、各种溶剂和其他的化学材料等,都会对空气、水体和土地造成污染,最终危害人体健康.尽管许多建筑师都对这些问题给予关注,却仅仅是象征性的——如果确实存在这种关注,其中包括一些国际知名的明星建筑师,如雷姆·库哈斯、弗兰克·盖里和丹尼尔·里伯斯金等.真正令人看到希望的迹象都来自于年轻的建筑师,尤其规模较小的事务所中的一些更有创意的员工.     

Expressing through digital photographs: an assistive tool for persons with aphasia

This paper describes the design of an assistive tool called CoCreation that can help people with aphasia to express daily experiences by utilizing digital photographs. CoCreation can upload the user’s pictures and can cluster them as a function of the time at which the pictures were taken. Pictures taken within a short period of time are assumed to highlight a single activity. The user is able to select a cluster and can edit the pictures by dragging icons or drawing on top of them, or by typing words to create a caption. The pictures set the context for a story, while the additional tools such as keyboard and drawing pad allow the user to add information that is considered useful for sharing the experience. The paper presents the detailed design process and the preliminary evaluation of CoCreation with an experienced speech therapist.     

Design of a suitable production management system for a manufacturing company

This paper reports on the design of a suitable production management system (PMS) for a manufacturing company, located in Western Australia. The company was experiencing problems in scheduling and plant layout leading to further problems in materials flow, labour control, inventory and purchasing, material handling system, and production space.

Group technology (GT) was used to design a new plant layout. A G.T. algorithm was developed to minimise machine duplications. A Kanban system was designed to assist execution of scheduling based on a pull system. The design was tested by simulation using actual data collected on existing operations.     

Zwitterion‐Functionalized Detonation Nanodiamond with Superior Protein Repulsion and Colloidal Stability in Physiological Media

Nanodiamond (ND) is a versatile and promising material for bioapplications. Despite many efforts, agglomeration of nanodiamond and the nonspecific adsorption of proteins on the ND surface when exposed to biofluids remains a major obstacle for biomedical applications. Here, the functionalization of detonation nanodiamond with zwitterionic moieties in combination with tetraethylene glycol (TEG) moieties immobilized by click chemistry to improve the colloidal dispersion in physiological media with strong ion background and for the simultaneous prevention of nonspecific interactions with proteins is reported. Based on five building blocks, a series of ND conjugates is synthesized and their performance is compared in biofluids, such as fetal bovine serum (FBS) and Dulbecco's modified Eagle medium (DMEM). The adsorption of proteins is investigated via dynamic light scattering (DLS) and thermogravimetric analysis. The colloidal stability is tested with DLS monitoring over prolonged periods of time in various ratios of water/FBS/DMEM and at different pH values. The results show that zwitterions efficiently promote the anti‐fouling properties, whereas the TEG linker is essential for the enhanced colloidal stability of the particles.     

Comparison of clustering approaches with application to dual colour protein data

Cells communicate with their environment via proteins, located at the plasma membrane separating the interior of a cell from its surroundings. The spatial distribution of these proteins in the plasma membrane under different physiological conditions is of importance, since this may influence their signal transmission properties. In this study, the authors compare different methods such as hierarchical clustering, extensible Markov models and the gammics method for analysing such a spatial distribution. The methods are examined in a simulation study to determine their optimal use. Afterwards, they analyse experimental imaging data and extend these methods to simulate dual colour data.Inspec keywords: proteins, molecular biophysics, cellular biophysics, biomembranes, Markov processes, bioinformatics, statistical analysisOther keywords: clustering approaches, dual colour protein data, cell communication, plasma membrane, spatial protein distribution, signal transmission, hierarchical clustering, extensible Markov models, gammics method, experimental imaging data     

ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke

Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2^wt) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP^wt) and its phosphorylation-deficient mutant RKIP^S153A, known inhibitors of the ERK1/2 signaling cascade. RKIP^wt and RKIP^S153A attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.     

Degradations‐ und Energieverhalten reaktiver Amin‐Lösungen bei der CO2‐Absorption/Desorption

Reactive absorption using aqueous amine solutions is the technically most feasible retrofit option for the separation of CO₂ from flue gases. Frequently discussed issues are the realization of a cost‐effective increase in efficiency in the sophisticated overall absorption process and the minimization of the energy demand for solvent regeneration under operating conditions. However, the influence of degradation phenomena on capacity and energy efficiency during the absorption‐regeneration cycles using blended monoethanolamine solutions has been less considered so far. The decrease in capacity depends in particular on time, temperature, O₂‐ and SO₂ concentration in the flue gas and has to be considered in plant design. Addition of degradation inhibitors decreases the energy requirements.     

Optimized Protocol for Proportionate CNS Cell Retrieval as a Versatile Platform for Cellular and Molecular Phenomapping in Aging and Neurodegeneration

Efficient purification of viable neural cells from the mature CNS has been historically challenging due to the heterogeneity of the inherent cell populations. Moreover, changes in cellular interconnections, membrane lipid and cholesterol compositions, compartment-specific biophysical properties, and intercellular space constituents demand technical adjustments for cell isolation at different stages of maturation and aging. Though such obstacles are addressed and partially overcome for embryonic premature and mature CNS tissues, procedural adaptations to an aged, progeroid, and degenerative CNS environment are underrepresented. Here, we describe a practical workflow for the acquisition and phenomapping of CNS neural cells at states of health, physiological and precocious aging, and genetically provoked neurodegeneration. Following recent, unprecedented evidence of post-mitotic cellular senescence (PoMiCS), the protocol appears suitable for such de novo characterization and phenotypic opposition to classical senescence. Technically, the protocol is rapid, efficient as for cellular yield and well preserves physiological cell proportions. It is suitable for a variety of downstream applications aiming at cell type-specific interrogations, including cell culture systems, Flow-FISH, flow cytometry/FACS, senescence studies, and retrieval of omic-scale DNA, RNA, and protein profiles. We expect suitability for transfer to other CNS targets and to a broad spectrum of engineered systems addressing aging, neurodegeneration, progeria, and senescence.