Light interactions with gold nanorods and cells: implications for photothermal nanotherapeutics

Gold nanorods (AuNR) can be tailored to possess an intense and narrow longitudinal plasmon (LP) absorption peak in the far-red to near-infrared wavelength region, where tissue is relatively transparent to light. This makes AuNRs excellent candidates as contrast agents for photoacoustic imaging, and as photothermal therapeutic agents. The favorable optical properties of AuNR which depend on the physical parameters of shape, size and plasmonic coupling effects, are required to be stable during use. We investigate the changes that are likely to occur in these physical parameters in the setting of photothermal therapeutics, and the influence that these changes have on the optical properties and the capacity to achieve target cell death. To this end we study 3 sets of interactions: pulsed light with AuNR, AuNR with cells, and pulsed light with cells incubated with AuNR. In the first situation we ascertain the threshold value of fluence required for photothermal melting or reshaping of AuNR to shorter AuNR or nanospheres, which results in drastic changes in optical properties. In the second situation when cells are exposed to antibody-conjugated AuNR, we observe using transmission electron microscopy (TEM) that the particles are closely packed and clustered inside vesicles in the cells. Using dark-field microscopy we show that plasmonic interactions between AuNRs in this situation causes blue-shifting of the LP absorption peak. As a consequence, no direct lethal damage to cells can be inflicted by laser irradiation at the LP peak. On the other hand, using irradiation at the transverse peak (TP) wavelength in the green, at comparative fluences, extensive cell death can be achieved. We attribute this behavior on the one hand to the photoreshaping of AuNR into spheres and on the other hand to clustering of AuNR inside cells. Both effects create sufficiently high optical absorption at 532 nm, which otherwise would have been present at the LP peak. We discuss implications of these finding on the application of these particles in biomedicine.     

Activity-based profiling of retaining β-glucosidases: a comparative study

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based profiling of glycosidases, on the other hand, has proven more difficult, and to date no broad-spectrum glycosidase activity-based probes (ABPs) have been reported. In a comparative study, we investigated both 2-deoxy-2-fluoroglycosides and cyclitol epoxides for their utility as a starting point towards retaining β-glucosidase ABP. We also investigated the merits of direct labeling and two-step bio-orthogonal labeling in reporting on glucosidase activity under various conditions. Our results demonstrate that 1) in general cyclitol epoxides are the superior glucosidase ABPs, 2) that direct labeling is the more efficient approach but it hinges on the ability of the glucosidase to be accommodated in the active site of the reporter (BODIPY) entity, and 3) that two-step bio-orthogonal labeling can be achieved on isolated enzymes but translating this protocol to cell extracts requires more investigation.     

The effect of partial replacement of carbon black by carbon nanotubes on the properties of natural rubber/butadiene rubber compound

The basic objective of this study is to investigate the mechanical properties of tyre tread compounds by gradual replacement of carbon black by multiwalled carbon nanotubes (MWCNTs) in a natural rubber–butadiene rubber‐based system. A rapid change in the mechanical properties is noticed even at very low concentrations of nanotubes though the total concentration of the filler is kept constant at 25 phr (parts per hundred rubber). The correlation of the bound rubber content with MWCNT loading directly supports the conclusion that MWCNTs increase the occluded rubber fraction. Transmission electron microscopy reveals a good dispersion of the MWCNT up to a certain concentration. In the presence of MWCNT, a prominent negative shift of the glass transition temperature of the compound is found. Thermal degradation behavior, aging, and swelling experiments were also carried out to understand the resulting effect of the incorporation of MWCNT in the rubber matrix. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3153–3160, 2013     

Testing software components for integration: a survey of issues and techniques

Component‐based development has emerged as a system engineering approach that promises rapid software development with fewer resources. Yet, improved reuse and reduced cost benefits from software components can only be achieved in practice if the components provide reliable services, thereby rendering component analysis and testing a key activity. This paper discusses various issues that can arise in component testing by the component user at the stage of its integration within the target system. The crucial problem is the lack of information for analysis and testing of externally developed components. Several testing techniques for component integration have recently been proposed. These techniques are surveyed here and classified according to a proposed set of relevant attributes. The paper thus provides a comprehensive overview which can be useful as introductory reading for newcomers in this research field, as well as to stimulate further investigation. Copyright © 2006 John Wiley & Sons, Ltd.     

Digital twin of composite assembly manufacturing process

Industry is facing the management of geometrical deviations along the entire lifecycle of the product. It is helped by digital twin tools that may minimise the geometrical deviations from nominal of products. The new digital twin tools allow to manage geometrical variations through a set of steps fully related by modern information and communication technologies that establish a continuous and unambiguous flow of information among the different steps of this digital process along the whole product lifecycle. They are based on data coming from manufacturing, assembly and inspection. The available large data sets from manufacturing and inspection allow to develop new and more accurate simulation models that realistically consider form deviations and process signature, i.e. the pattern left by the manufacturing process on the produced part surfaces. The present work introduces a digital twin tool to support the lightweight design of assemblies in composite material. It establishes a continuous and unambiguous flow of variation information from the part design to assembly, passing through manufacturing by considering the manufacturing signature. It was applied to a case study and the obtained results agree with the experimental ones.     

CSF Biomarkers Reflecting Protein Pathology and Axonal Degeneration Are Associated with Memory,Attentional, and Executive Functioning in Early-Stage Parkinson′s Disease

In early-stage Parkinson′s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF α-synuclein species, neurofilament light chain, amyloid-β₄₂, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-α-synuclein and phosphorylated-α-synuclein, neurofilament light chain, amyloid-β₄₂, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration ≤5 years and Hoehn and Yahr stage 1–2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-α-synuclein/total-α-synuclein ratio was associated with better executive functioning (sβ = 0.40). Higher CSF neurofilament light was associated with worse memory (sβ = −0.59), attentional (sβ = −0.32), and executive functioning (sβ = −0.35). Reduced CSF amyloid-β₄₂ levels were associated with poorer attentional functioning (sβ = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (sβ = −0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.     

Economic and epidemiological impact of different intervention strategies for clinical contagious mastitis

The overall aim of this study was to compare different intervention strategies for clinical intramammary infections (IMI). We conducted a simulation study to represent a Danish dairy cattle herd with IMI caused mostly by Staphylococcus aureus and 9 different intervention strategies for clinical IMI. A standard intervention of 3 d of treatment consisting of intramammary injections for all clinical cases was used. Two of the strategies reflected the use of more antibiotics and 6 strategies reflected cow-specific treatment or culling decisions. For these strategies, we assessed the cost and effectiveness of culling as an IMI intervention. Our results showed that nearly all strategies could reduce the number of IMI cases [e.g., a median of 37 clinical cases with the extended intramammary treatment over 5 d strategy (Basic5) and 30 clinical cases with the cow culled with recovery probability below 50% (Before50)] compared with the standard intervention (median of 42 clinical cases). This happened alongside either increased antibiotic usage (e.g., from a median of 123 treatment days up to 179 treatment days with strategy Basic5) or an increased number of cows culled in relation to IMI (e.g., from a median of 16 up to 24 cows with strategy Before50). Strategies with more antibiotics or reactive culling had a slightly higher net income (e.g., €190,014 median net income with strategy Basic5 or €196,995 with strategy Before50 compared with €187,666 with the standard strategy). This shows that a cow-specific clinical intervention approach can be cost-effective in reducing IMI incidence.     

Analysis of size distribution functions of diamond crystallites formed in the early stages of chemical vapour deposition

Size distribution functions of diamond particles formed in the early stages of chemical vapour deposition (CVD) can be used to distinguish between seeding and heterogeneous nucleation on the basis of their shape and of the d_max/d_min ratio, d_max and d_min being the maximum and the minimum diameters, respectively. A monomodal size distribution function with a d_max/d_min ratio much greater than 1.2–1.3 indicates diamond formation to occur via heterogeneous nucleation. In this case the nucleation kinetics can be calculated once the growth law of the crystallites has been established. The nucleation kinetics at copper substrates have been derived from distribution functions and described by a new kinetic model which includes the generation of nucleation sites.     

Formulating characteristics of high and low 2-phenyl linear alkylbenzene sulfonates in liquid detergents

Detergent range linear alkylbenzene (LAB) currently is manufactured by two different processes, using either aluminum chloride or hydrogen fluoride as the alkylation catalyst. The alkylates from the two processes are not exactly the same. Furthermore, the properties of the linear alkylbenzene sulfonate (LAS) surfactants made by sulfonation of the LABs also differ. Because LAS is used in most types of detergent products, it is important to known how the properties of each type of LAS differ. This paper compares the formulating characteristics (such as viscosity, solubility and foaming) of high and low 2-phenyl LAS in some typical household cleaning product formulations. It is concluded that the two types of LAS should not be used interchangeably without first checking carefully all the physical properties required in a product. Presented at the AOCS meeting in Honolulu, Hawaii in May 1986.     

Inhibition of RNA synthesis in vitro by acridines--relation between structure and activity

The effects of acridine derivatives (proflavine and 2,7-dialkyl derivatives, diacridines and triacridines, 9-aminoacridine carboxamides, and 9-anilinoacridine, amsacrine and its congeners) on overall RNA synthesis in vitro, on synthesis of initiating oligonucleotides and the binding of the enzyme to DNA were studied. The primary mechanism of action is related to inhibition of the enzyme binding to DNA. The acridines (intercalating or non-intercalating and bis-intercalating ligands) assayed here differ in the properties of their complexes with DNA. Correlation is generally observed between inhibition of RNA synthesis in vitro and cytotoxicity in cell cultures for di- and triacridines and 9-aminoacridine carboxamide derivatives. No relationship was found between the effect on RNA polymerase system and biological effects for amsacrine and its derivatives in contrast to the other series of acridines studied here. The aniline ring seems to decrease the inhibitory potency of a ligand. The discrepancy between the biological effect and RNA synthesis inhibition may be due to a different mechanism of cytotoxicity action of amsacrine which is a potent topoisomerase II poison.