The encapsulation of gold nanoparticles using RAFT, ATRP and miniemulsion polymerisation techniques

The investigation into the encapsulation of gold nanoparticles (AuNPs) by poly(methyl methacrylate) (PMMA) was undertaken. This was performed by three polymerisation techniques including: grafting PMMA synthesised by reversible addition-fragmentation chain transfer (RAFT) polymerisation to AuNPs, grafting PMMA synthesised by atom transfer radical polymerisation (ATRP) from the surface of functionalised AuNPs and by encapsulation of AuNPs within PMMA latexes produced through photo-initiated oil-in-water (o/w) miniemulsion polymerisation. The grafting of RAFT PMMA to AuNPs was performed by the addition of the RAFT functionalised PMMA to citrate stabilised AuNPs. This was conducted with a range of PMMA of varying molecular weight distribution (MWD) as either the dithioester or thiol end-group functionalities. The RAFT PMMA polymers were characterised by gel permeation chromatography (GPC), ultraviolet-visible (UV-vis), Fourier transform infrared-attenuated total reflectance (FTIR-ATR), Fourier transform Raman (FT-Raman) and proton nuclear magnetic resonance (1H NMR) spectroscopies. The attachment of PMMA to AuNPs showed a tendency for AuNPs to associate with the PMMA structures formed, though significant aggregation occurred. Interestingly, thiol functionalised end-group PMMA showed very little aggregation of AuNPs. The spherical polymer-AuNP structures did not vary in size with variations in PMMA MWD. The PMMA-AuNP structures were characterised using scanning electron microscopy (SEM), transition electron microscopy (TEM), energy dispersive X-ray analysis (EDAX) and UV-vis spectroscopy. The surface confined ATRP grafting of PMMA from initiator functionalised AuNPs was polymerised in both homogeneous and heterogeneous media. 11,11’- dithiobis[1-(2-bromo-2-methylpropionyloxy)undecane] (DSBr) was used as the surface-confined initiator and was synthesised in a three step procedure from mercaptoundecanol (MUD). All compounds were characterised by 1H NMR, FTIR-ATR and Raman spectroscopies. The grafting in homogeneous media resulted in amorphous PMMA with significant AuNP aggregation. Individually grafted AuNPs were difficult to separate and characterise, though SEM, TEM, EDAX and UV-vis spectroscopy was used. The heterogeneous polymerisation did not produce grafted AuNPs as characterised by SEM and EDAX. The encapsulation of AuNPs within PMMA latexes through the process of photoinitiated miniemulsion polymerisation was successfully achieved. Initially, photoinitiated miniemulsion polymerisation was conducted as a viable low temperature method of miniemulsion initiation. This proved successful producing a stable PMMA with good conversion efficiency and narrow particle size distribution (PSD). This is the first report of such a system. The photo-initiated technique was further optimised and AuNPs were included into the miniemulsion. AuNP encapsulation was very effective, producing reproducible AuNP encapsulated PMMA latexes. Again, this is the first reported case of this. The latexes were characterised by TEM, SEM, GPC, gravimetric analysis and dynamic light scattering (DLS).

The patella morphology in trochlear dysplasia : a comparative MRI study

BACKGROUND: Trochlear dysplasia is suspected to have a genetic basis and causes recurrent patellar instability due to insufficient anatomical geometry. Numerous studies about trochlear morphology and the optimal surgical treatment have been carried out, but no attention has been paid to the corresponding patellar morphology.----- ----- PURPOSE: The aim of this study was the evaluation of the patellar morphology in normal and trochlear dysplastic knees. ----- ----- STUDY DESIGN: Biometric analysis. ----- ----- METHODS: Twenty two patellae with underlying trochlear dysplasia (study group--SG) were compared with 22 matched knees with normal trochlear shape (control group--CG) on transverse and sagittal MRI slices. We compared transverse diameter, cartilaginous thickness, Wiberg-index and -angle, length and radius of lateral and medial facet, patellar shape and angle, retropatellar length, and type of trochlear dysplasia. For statistical analysis we used the Wilcoxon signed ranks test. ----- ----- RESULTS: The transverse and sagittal diameter, mean length of medial patellar facet, and mean cartilaginous and subchondral Wiberg-index showed statistical differences between the two groups. ----- ----- CONCLUSIONS: Although the insufficient trochlear depth and decreased lateral trochlear slope are responsible for patellofemoral instability, the patella shows morphological changes in trochlear dysplastic knees. Its overall size and the medial facet are smaller. Although the femoral sulcus angle is larger, the Wiberg-angle and -index are equal to the control group. This may indicate that the patellar morphology may not be a result of missing medial patellofemoral pressure in trochlear dysplastic knees, but a decreased medial patellofemoral traction. This seems to be caused by hypotrophic medial patellofemoral restraints in combination with an increased lateral patellar tilt, both resulting in a decreased tension onto the medial patella facet. Whether there is a genetic component to the patellar morphology remains open.

Poorly characterized phases in C2M carbonaceous chondrites : proposed structures and significance

Poorly characterized phases (PCP's) may constitute up to 30 volume percent of some C2M carbonaceous chondrite matrices [1] and are an important key to an understanding of matrix evolution. PCPs are usually fine-grained (Fuchs et al. [2] introduced the term PCP in their detailed description of Fe-S-Ni-0 phases in the matrix of Murchison. Ramdohr [3] described a similar Fe-S-C phase with trace amounts of Ni in five carbonaceous chondrites and proposed that this mineral has a layer structure. Both the Fe-S-Ni-0 and Fe-S-Ni-C phases have similar optical properties and are conveniently described by the generic term PCP [1]. On the basis of recent high resolution electron microscopy (HREM) studies [4-9], we propose that these PCP's form at least two ordered, stable structures based upon alternating sequences of mackinawite- and brucite- (or amakinite-) type layers.

Human-centric process-aware information systems (HC-PAIS)

Process-Aware Information Systems (PAIS) support organizations in managing and automating their processes. A full automation of processes is in particular industries, such as service-oriented markets, not practicable. The integration of humans in PAIS is necessary to manage and perform processes that require human capabilities, judg- ments and decisions. A challenge of interdisciplinary PAIS research is to provide concepts and solutions that support human integration in PAIS and human orientation of PAIS in a way that provably increase the PAIS users' satisfaction and motivation with working with the Human-Centric Process Aware Information System (HC-PAIS) and consequently in uence users' performance of tasks. This work is an initial step of research that aims at providing a definition of Human-Centric Process Aware Information Systems (HC-PAIS) and future research challenges of HC-PAIS. Results of focus group research are presented.

Soziale Medien in Krisensituationen

Vom Oderhochwasser über Hurricane Sandy bis zum Tsunami und Reaktormeltdown an der japanischen Ostküste: die letzten Jahre waren leider reich an Naturkatastrophen und anderen Krisensituationen, welche Hunderttausende von Menschen betroffen haben. Abgesehen davon, daß viele dieser Krisen auch die ersten Auswirkungen des Klimawandels greifbar gemacht haben, verdeutlichen sie auch eine andere, ebenfalls nicht unwichtige Form des Wandels: die graduelle Umgestaltung der Medienlandschaft, in der herkömmliche Massenmedien vermehrt durch soziale Medien wie Facebook oder Twitter ergänzt und teilweise vielleicht sogar ersetzt werden.

Strategic IMC : from abstract concept to marketing management tool

Although integrated marketing communication (IMC) has progressed towards midrange maturity level, its full-scale adoption has been impeded by a lack of consensus on its defining constructs. The purpose of this study is to move from abstraction to define the construct of strategic integration (SI) and develop this into a management tool, thus making an important contribution to both the theory and practice of IMC. Drawing from both IMC and strategic management literature, the construct of SI is operationalised into a number of key factors and a well-cited management model, Fuchs’ ‘integration valuator’ is explored as the starting point of a measurement tool for IMC. To do this, a Delphi study invites the scrutiny of an expert panel of world-leading IMC researchers and practitioners. The panel validated the model construction process,redefined overarching constructs and key factors with a high degree of consensus, supported a process measure, suggested a weighted evaluation measure and recognised the importance of developing such a measure. They delivered clear and consistent imperatives guiding model development. The result is a measure of SI that evaluates organisational proficiency and diagnoses the integration of IMC campaigns. It also advances theory by providing a better understanding of the construct of SI.

Augmenting and assisting model elicitation tasks with 3D virtual world context metadata

Accurate process model elicitation continues to be a time consuming task, requiring skill on the part of the interviewer to extract explicit and tacit process information from the interviewee. Many errors occur in this elicitation stage that would be avoided by better activity recall, more consistent specification methods and greater engagement in the elicitation process by interviewees. Theories of situated cognition indicate that interactive 3D representations of real work environments engage and prime the cognitive state of the viewer. In this paper, our major contribution is to augment a previous process elicitation methodology with virtual world context metadata, drawn from a 3D simulation of the workplace. We present a conceptual and formal approach for representing this contextual metadata, integrated into a process similarity measure that provides hints for the business analyst to use in later modelling steps. Finally, we conclude with examples from two use cases to illustrate the potential abilities of this approach.

Development of a polymer theranostic for prostate cancer

Theranostics offers an improved treatment strategy for prostate cancer by facilitating simultaneous targeting of tumour cells with subsequent drug delivery and imaging. In this report we describe the synthesis of hyperbranched polymers that are biocompatible, can specifically target and be internalised by prostate cancer cells (through targeting of prostate-specific membrane antigen – PSMA) and ultimately facilitate controlled delivery of a model drug. The theranostic also incorporates a far-red fluorescent dye that allows tracking of the polymer via optical imaging. Controlled synthesis of the polymer is achieved via reversible addition fragmentation chain transfer polymerisation of polyethylene glycol monomethyl methacrylate, with ethylene glycol dimethacrylate as the branching agent. Incorporation of 20 mol% of an hydrazide-methacrylate monomer allows post-ligation of a model drug, fluorene-2-carboxaldehyde, through a hydrolytically-degradable hydrazone linkage. The rate of degradation of this particular linker was enhanced at endosomal pH (pH = 5.5) where [similar]95% of the model drug was released in 4 hours compared to less than 5% released over the same period at physiological pH. The theranostic showed high uptake into prostate cancer cells expressing prostate-specific membrane antigen, while minimal uptake was observed in PC3 cells negative for PSMA, highlighting the enhanced efficacy of the targeting ligand.

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan–hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5 h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8 h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8 h to 24 h post-administration compared to the free NPs, due to a NP ‘guarding’ effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24 h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.

Acute infectious diarrhea lessons learned from the past?

The Journal of Pediatric Gastroenterology and Nutrition (JPGN) has been at the forefront of many of the seminal advances into research on infectious diarrhea. In 1982, the first article of the JPGN was entitled “Oral Therapy for Dehydration in Diarrheal Diseases as a Global Problem” and has set the scene for several thousand subsequent articles. In his initial editorial, Finberg (1) posed several questions, which still have relevance 30 years later: 1. When is oral rehydration not appropriate, if ever? 2. What should be the composition of the oral solution and should there be more than one? 3. Should recommended practice be different in lesser-developed countries from those in developed countries? 4. Should the salts and glucose be prepackaged or should home supplies be used by instructed mothers? 5. When should standard feedings be resumed?

Evaluation of polymeric nanomedicines targeted to PSMA: Effect of ligand on targeting efficiency

Targeted nanomedicines offer a strategy for greatly enhancing accumulation of a therapeutic within a specific tissue in animals. In this study, we report on the comparative targeting efficiency toward prostate-specific membrane antigen (PSMA) of a number of different ligands that are covalently attached by the same chemistry to a polymeric nanocarrier. The targeting ligands included a small molecule (glutamate urea), a peptide ligand, and a monoclonal antibody (J591). A hyperbranched polymer (HBP) was utilized as the nanocarrier and contained a fluorophore for tracking/analysis, whereas the pendant functional chain-ends provided a handle for ligand conjugation. Targeting efficiency of each ligand was assessed in vitro using flow cytometry and confocal microscopy to compare degree of binding and internalization of the HBPs by human prostate cancer (PCa) cell lines with different PSMA expression status (PC3-PIP (PSMA+) and PC3-FLU (PSMA−). The peptide ligand was further investigated in vivo, in which BALB/c nude mice bearing subcutaneous PC3-PIP and PC3-FLU PCa tumors were injected intravenously with the HBP-peptide conjugate and assessed by fluorescence imaging. Enhanced accumulation in the tumor tissue of PC3-PIP compared to PC3-FLU highlighted the applicability of this system as a future imaging and therapeutic delivery vehicle.