Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia

We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.     

Fast mass transport through carbon nanotube membranes

The May 19, 2006 issue of Science included a paper by Holt et al. on "Fast Mass Transport Through Sub-2-Nanometer Carbon Nanotubes". The paper was also featured on the cover, showing methane molecules translating inside a carbon nanotube (CNT). The authors explained how they prepared 2-6-mum thin membranes consisting of double-walled carbon nanotubes (DWNTs) all aligned perpendicular to the apparent membrane surface. These tubes are open at both ends and the space between the tubes is filled with dense Si(3)N(4). Pure gas and water fluxes were measured at room temperature with the application of a small pressure difference. Interpretation of the results led to the conclusion that the membranes showed much higher fluxes than what was estimated from Knudsen gas diffusion and Poiseuille viscous flow models. The membranes have a straight-channel morphology with a narrow pore-size distribution and exceptionally smooth pore walls. The unusual geometry and surface properties make it difficult to compare the membrane's properties with common membranes but there is no question that the mass transport in the aligned DWNTs is fast indeed. To appreciate how fast, we will consider their transport properties starting from the perspective of "conventional" porous membrane technology. Recent molecular dynamics simulations suggest that none of the classic models for gas (Knudsen) and water (Poiseuille) permeation work in a meaningful way for these nanotube membranes, and new models are needed.     

Pathogenic potential of Salmonella Typhimurium DT104 following sequential passage through soil, packaged fresh-cut lettuce and a model gastrointestinal tract

From a quantitative microbial risk assessment perspective it is important to know whether certain food environments influence the pathogenic potential of pathogens and to what extent. The purpose of the present study was to examine the pathogenic potential of S. Typhimurium DT104, measured as the capability to survive a simulated gastrointestinal tract system and the capability of adhering to and invading differentiated Caco-2 cells, after sequential incubation (without intermediate culturing) into soil, lettuce and cut lettuce stored under modified atmosphere (MAP) conditions. Two S. Typhimurium DT104 strains were used, one isolated from a pig carcass and one isolated from lettuce. The most important result of the present study is that the sequential incubation of S. Typhimurium in soil and lettuce slightly increased the capability of surviving the simulated gastric fluid, increased the capability to grow in the simulated intestinal fluid but decreased the capability of epithelial attachment and invasion and decreased the overall survival probability of the gastrointestinal tract system. Some variation in responses between the strains was observed, with the lettuce strain maintaining higher epithelial attachment capability and the carcass strains maintaining higher epithelial invasion capability. This study provided quantitative data on the effect of environmental and food matrices on the pathogenic potential of S. Typhimurium DT104 using a realistic system of sequential incubations in environmental and food matrices, followed by simulated gastrointestinal tract passage without intermediate culturing. These results could aid the development of more realistic quantitative microbial risk assessments.     

Slow and very slow desorption of organic compounds from sediment: influence of sorbate planarity

The kinetics of desorption of in situ chlorobenzenes, PAHs, and PCBs from four different sediments was studied employing Tenax beads as an infinite sink for sorbates. Rate constants for slow desorption were 2.9+/-0.4 x 10(-2) x h(-1), irrespective of the extent of sorbate planarity. Rate constants for very slow desorption were 2.1+/-0.5 x 10(-4) and 6.7+/-1.4 x 10(-4) x h(-1) for planar and non-planar compounds, respectively. Comparison with literature data suggests a priori estimates for rate constants for slow desorption to be 3 x 10(-2) x h(-1), and to be 2 x 10(-4) and 7 x 10(-4) x h(-1) for very slow desorption of planar and non-planar compounds, respectively. The ratio between the fractions in the very slowly desorbing domain and the rapidly desorbing domain was 15-38 for planar compounds which is higher than for non-planar compounds for which the ratio was 2.8-5.2. The ratio between the fractions in the slowly desorbing domain and the rapidly desorbing domain was 1.3-1.8 and independent of the sorbate planarity. The difference in influence of sorbate planarity on the very slowly desorbing domain as compared to the slowly desorbing domain points to different environments for the slowly and the very slowly desorbing fractions.     

The development of a method to measure speed adaptation to traffic complexity: identifying novice, unsafe, and overconfident drivers

To monitor novice driver performance in the first years of solo driving, a test aimed at assessing speed adaptation to the traffic situation was developed and evaluated. The Adaptation Test consisted of 18 traffic scenes presented in two (almost) identical photographs, which differed in one single detail, increasing the situation's complexity. As the pictures were presented randomly and participants could not return to previous pictures, participants were kept unaware of the complexity differences in the pictures. The difference in reported speed between the two pictures was used as an indication of drivers' inclination to adapt their speed to the complexity of the traffic situation. Results showed that novice drivers (n=434) performed worse on the Adaptation Test (i.e. less often reported a lower speed in the more complex situation) than experienced drivers (n=173). In addition, unsafe drivers and overconfident drivers, as identified in an on-road driving assessment, performed worse on the Adaptation Test. This indicates that the Adaptation Test is effective at measuring adaptation of driving speed to the complexity of the situation; and that incorrect self-assessment, and overestimating driving skills in particular, may have a negative effect on speed adaptation.     

Structural features and properties of soluble products derived from Eucalyptus globulus hemicelluloses

Eucalyptus globulus wood samples were subjected to double hydrothermal processing to remove extractives in the first stage, and to cause the selective solubilisation of 4-O-methylglucuronoxylan in the second stage. The hemicellulose-derived products present in the liquors from the second hydrothermal stage (substituted xylooligosaccharides, denoted XOS) were refined by treatments with membranes and ion exchange. The purified XOS product was assayed for composition and characterised by HPLC-RI, HPAEC-PAD, HPSEC, MALDI-TOF-MS and NMR techniques. The results suggested the presence of neutral and acidic XOS with a degree of acetylation of about 0.6. The fermentability of the refined XOS product by faecal inocula was assessed by measuring both substrate consumption and formation of short-chain fatty acids.     

Discovery of a New Class of Non‐imidazole Oxazoline‐Based Histamine H3 Receptor (H3R) Inverse Agonists

H ₃ R inverse agonists based on an aminopropoxy‐phenyloxazoline framework constitute highly valuable druglike lead compounds that display efficacy in a mouse model of recognition memory.

     

Exploring Chemical Substructures Essential for hERG K+ Channel Blockade by Synthesis and Biological Evaluation of Dofetilide Analogues

In this study we followed a new approach to analyze molecular substructures required for hERG channel blockade. We designed and synthesized 40 analogues of dofetilide ( 1 ), a potent hERG potassium channel blocker, and established structure–activity relationships (SAR) for their interaction with this important cardiotoxicity‐related off‐target. Structural modifications to dofetilide were made by diversifying the substituents on the phenyl rings and the protonated nitrogen and by varying the carbon chain length. The analogues were evaluated in a radioligand binding assay and SAR data were derived with the aim to specify structural features that give rise to hERG toxicity.     

Nylon 6 polymerization in the solid state

The postcondensation of nylon 6 in the solid state was studied. The reactions were carried out on fine powder in a fluidized bed reactor in a stream of dry nitrogen in the temperature range 110–205°C and during 1–24 h. The solid-state polymerization (SSP) did not follow melt kinetics, but was found to be limited by the diffusion of the autocatalyzing acid chain end group. Factors thought to influence SSP were studied, e.g., heat treatment, starting molecular weight, and remelting. Surprisningly, heat treatment had little effect, but the starting molecular weight had a strong effect on the reaction rate. The higher the starting molecular weight, the faster the reaction. This could be explained as a changing concentration distribution of the reactive groups in the solid state on SSP. The kinetics of the SSP had more than one region, and the rate of reaction for conversions of over 30% could be expressed as ? dc/dt = k(c/t), where k is a dimensionless constant independent of temperature with a value of 0.28. The integrated form has the form ? In(c/c_o) = k In(t/τ), where c_o is the acid end-group concentration at the start, t is the reaction time, and τ is the induction time. The value of τ is both dependent on the starting concentration c_o and the reaction temperature and has an activation energy of 105 kJ/mol.