Apparent Complete Response of a Treatment Refractory and Recurrent Squamous Cell Carcinoma Lesion to Photochemical Internalization: A Clinical Case Study

Photochemical internalization (PCI) depends on the delivery of sublethal photodynamic reaction to facilitate the work of a chemotherapeutic agent. We discuss our experience in managing a patient with extensive squamous cell carcinoma of the right face and scalp under the TPCS_2a-based bleomycin PCI treatment protocol. In this case, an 84-year-old Caucasian received 0.25 mg kg⁻¹ of TPCS_2a (Amphinex^®, PCI Biotech AS, Oslo, Norway). Surface illumination photochemical internalization was carried out after 4 days, which was preceded by the chemotherapeutic agent infusion (Bleomycin). After one week from the illumination time, tissue necrosis was evident and tumor shrinkage was most noticeable at day 14 postillumination. Follow-up at 6 weeks continued to show tissue healing and regeneration with no clinical evidence of recurrence. Multiple surgical biopsies were taken at 1 and 3 months postillumination and found to be tumor free. PCI’s depth of effect has been very significant with negligible damage to the collateral tissues. This technology has a role in interventional oncology especially when managing challenging cases.     

Determination of lead and cadmium in seawater using a vibrating silver amalgam microwire electrode

Silver amalgamated electrodes are a good substrate to determine lead (Pb) and cadmium (Cd) in seawater because they have properties similar to mercury but without the free mercury (Hg). Here a silver amalgamated microwire (SAM) electrode is optimised for the determination of Pb and Cd in coastal waters and uncontaminated ocean waters. The SAM was vibrated during the deposition step to increase the sensitivity, and electroanalytical parameters were optimised. The Hg coating required plating from a relatively concentrated (millimolar) solution, much greater (500×) than used for instance to coat glassy carbon electrodes. However, the coating on the ex situ amalgamated electrode was found to be stable and could be used for up to a week to determine trace levels of Pb in seawater of natural pH. The limit of detection square-wave ASV (50 Hz) using the pre-plated SAM electrode was 8 pM Pb using a 1-min plating time at pH 4.5. The limit of detection in pH 2 seawater was 4 pM using a 5-min plating time, and it was 12 pM using a 10-min plating time at natural pH in the presence of air, using a square-wave frequency of 700 Hz. The vibrating SAM electrode was tested on the determination of Pb in reference seawater samples from the open Atlantic (at the 20 pM level), Pacific, and used for a study of Pb in samples collected over 24 h in Liverpool Bay (Irish Sea).     

Non‐Invasive Monitoring of Osteogenic Differentiation on Microtissue Arrays under Physiological Conditions Using Scanning Electrochemical Microscopy

In this paper, we present a non‐invasive assay using scanning electrochemical microscopy (SECM) for detecting osteogenic differentiation at physiological conditions (pH 7.5) on arrays of C2C12 microtissues. Upon exposure to bone morphogenic protein 2 (BMP‐2), C2C12 microtissues differentiate and express alkaline phosphatase (ALP), which is indirectly detected through an enzymatic assay producing an electroactive species. The latter is detected using SECM by scanning at constant height over live microtissues at physiological pH (7.5) as well as more alkaline pH (8.5). As a control, expression of ALP is confirmed using a standard colorimetric assay. Detecting differentiation on live samples at physiological conditions represents a significant improvement for continuous monitoring of tissue differentiation or further use of the microtissues for, e.g., regenerative medicine.     

Metabolomics data exploration guided by prior knowledge

In metabolomics research, it is often important to focus the data analysis to specific areas of interest within the metabolome. In this paper, we describe the application of consensus principal component analysis (CPCA) and canonical correlation analysis (CCA) as a means to explore the relation between metabolome data and (i) biochemically related metabolites and (ii) an amino acid biosynthesis pathway. CPCA searches for major trends in the behavior of metabolite concentrations that are in common for the metabolites of interest and the remainder of the metabolome. CCA identifies the strongest correlations between the metabolites of interest and the remainder of the metabolome.CPCA and CCA were applied to two different microbial metabolomics data sets. The first data set, derived from Pseudomonas putida S12, was relatively simple as it contained metabolomes obtained under four environmental conditions only. The second data set, obtained from Escherichia coli, was much more complex as it consisted of metabolomes obtained under 28 different environmental conditions. In case of the simple and coherent P. putida S12 data set, CCA and CPCA gave similar results as the variation in the subset of the selected metabolites and the remainder of the metabolome was similar.In contrast, CCA and CPCA yielded different results in case of the E. coli data set. With CPCA the trends in the selected subset - the phenylalanine biosynthesis pathway - dominated the results. The main trends were related to high and low phenylalanine productivity, and the metabolites showing a similar behavior in concentration were metabolites regulating the phenylalanine biosynthesis route in the subset and metabolites related to general amino acid metabolism in the remainder of the metabolome. With CCA, neither subset truly dominated the data analysis. CCA described the differences between the wild type and the overproducing strain and the differences between the succinate and glucose grown cells. For the difference between the wild type and the overproducing strain, metabolites from the beginning and the end of aromatic amino acid pathways like erythrose-4-phosphate, tryptophan, and phenylalanine were important for the selected metabolites.CCA and CPCA proved to be complementary data analysis tools that enable the focusing of the data analysis on groups of metabolites that are of specific interest in relation to the remainder of the metabolome. Compared to an ordinary PCA, focusing the data analysis on biologically relevant metabolites lead especially for the complex E. coli data to a better biological interpretation of the data.     

Synthesis and evaluation of dimeric lipophilic iminosugars as inhibitors of glucosylceramide metabolism

Four dimeric and four monomeric lipophilic iminosugars were synthesized and subsequently evaluated on their inhibitory potential towards mammalian glucosylceramide synthase, glucocerebrosidase, β-glucosidase 2, sucrase and lysosomal α-glucosidase. Compared to their monomeric counterparts the dimeric inhibitors showed decreased inhibition of glucosylceramide synthase and generally a comparable inhibitory potency for the glycosidases.     

Insensitive bounds for the moments of the sojourn time distribution in the M/G/1 processor-sharing queue

This paper studies the M/G/1 processor-sharing (PS) queue, in particular the sojourn time distribution conditioned on the initial job size. Although several expressions for the Laplace-Stieltjes transform (LST) are known, these expressions are not suitable for computational purposes. This paper derives readily applicable insensitive bounds for all moments of the conditional sojourn time distribution. The instantaneous sojourn time, i.e., the sojourn time of an infinitesimally small job, leads to insensitive upper bounds requiring only knowledge of the traffic intensity and the initial job size. Interestingly, the upper bounds involve polynomials with so-called Eulerian numbers as coefficients. In addition, stochastic ordering and moment ordering results for the sojourn time distribution are obtained. AMS Subject Classification: 60K25, 60E15 This work has been partially funded by the Dutch Ministry of Economic Affairs under the program ‘Technologische Samenwerking ICT-doorbraakprojecten’, project TSIT1025 BEYOND 3G.