Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.     

Study of the copper leaching in the wet oxidation of phenol with CuO-based catalysts: Causes and effects

Catalytic wet oxidation of phenol as a model pollutant has been performed in a three phase fixed-bed reactor (FBR) by using a commercial catalyst based on copper oxide in order to analyze the variables affecting significantly the copper leaching. It has been found that temperature has an almost negligible influence in the range studied (70–160 °C). On the contrary, an important effect of the pH value was noticed. The copper leaching reduces when the pH of the solution fed to the reactor increases, being almost negligible at pH ≥ 5. Moreover, the composition of the reaction media also influences the leaching. Higher copper concentrations than those expected by the effect of the acid aqueous media have been measured in the reactor effluent when phenol, catechol, hydroquinone, p-benzoquinone and maleic acid are present in the reaction media. On the contrary, oxalic acid has a negative influence on the leaching, since it captures the copper in solution to form copper oxalate which precipitates on the catalyst surface. For a previously acidified medium, the acetic and formic acids do not have any other effect on the copper leaching. It has been also demonstrated that as copper in solution decreases, so does phenol conversion, because the homogeneous catalysis contributes significantly to the oxidation reactions even in fixed-bed reactors.     

Rheological properties of ethylcellulose latex

Because of their large specific surface area, aqueous‐based pseudolatex systems of ethylcellulose can absorb large amounts of drugs. In addition, the stability of polymeric particles in biological fluids delays the release of the drug as in controlled drug delivery systems. The aim of the present study was to characterize the rheological properties of latex particles as a measure of their colloidal stability. Here, we report the effect of three variables: pH, electrolyte concentration, and temperature. The rheograms clearly show that the polymer suspensions displayed Bingham plastic behavior. Internal structuring of the latex was greatest at acid and natural pH values, particularly at the highest ionic strength. In acid solutions, only temperature appeared to play a fundamental role; both the shear stress corresponding to the onset of nonlinear viscoelasticity and the elastic modulus at all frequencies were higher at 37°C than those at room temperature. This is assumed to be a consequence of deformation of the polymer particles upon heating. The effect of ionic strength was noticeable only at the natural pH (pH ? 6.5). At high concentrations of sodium chloride, the particles aggregated because of the decrease in double layer repulsion, and as a result, the latex became structured and its elastic modulus subsequently increased. Interestingly, when the temperature was increased further, this structure presumably broke, down, at least partially, and the storage modulus was reduced. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 847–851, 2006     

Pd deposited on Cu(110): a highly performant catalyst for the 1,3-butadiene hydrogenation reaction

The catalytic properties, with respect to the 1,3-butadiene hydrogenation reaction, of strained Pd films on Cu(110) (lattice mismatch 8%) has been probed as a function of the film thickness. The characterization of the adlayer has been made by the combined use of STM with LEED and AES. For deposits below 10¹⁵ Pd/cm² (i.e., about 1 ML) the catalytic activity is near zero. This is the consequence of the formation of a Pd–Cu surface alloy with tendency for Cu to migrate/segregate to the surface. The catalytic activity suddenly increases to reach a maximum value for about 3 ML; the activity is then one order of magnitude higher than that of the pure Pd(110) surface. This is the consequence of the presence of a strained Pd overlayer, with Pd surface atoms having very unusual geometry, and hence very peculiar electronic and chemical properties. The catalytic activity then decreases as the Pd coverage is increased, and tends to values near that of the pure Pd(110). Gradual relaxation of the film geometry towards that of the normal fcc Pd structure probably exists.     

Carbohydrate type and amount alter intravascular processing and catabolism of plasma lipoproteins in guinea pigs

To test the effects of exchanging dietary complex and simple carbohydrate for fat calories on lipoprotein metabolism, guinea pigs were fed two different fat/carbohydrate ratios: 2.5∶58% (w/w) or 25∶29% (w/w) with either sucrose or starch as the carbohydrate source. Animals fed high-fat had higher plasma low-density lipoprotein (LDL) and hepatic cholesterol concentrations than animals fed low-fat diets (P<0.01). The cholesteryl ester content per particle was higher, and the number of triacylglycerol (TAG) molecules was lower in very low density lipoprotein (VLDL) and LDL from animals fed high-fat diets. Intake of high-fat/sucrose resulted in higher plasma LDL concentrations than intake of high-fat/starch, and animals fed low-fat/starch had the highest plasma TAG concentrations associated with VLDL particles containing more TAG molecules, as well as a TAG-enriched LDL. The activity of plasma lecithin cholesteryl:acyl transferase (LCAT) was highest in animals fed high-fat/sucrose, and heart lipoprotein lipase (LPL) activity was higher in animals fed high-fat diets. Hepatic apoprotein B/E (apo B/E) receptor number (B_max) was increased 21% with low-fat diets (P<0.01). These results suggest that the hypercholesterolemia induced by high-fat and by sucrose intake are associated with a higher plasma LCAT activity which results in a cholesteryl ester-enriched VLDL which, by the action of LPL, might be more readily converted to LDL through the delipidation cascade leading to downregulation of hepatic apo B/E receptors. The hypertriglyceridemia associated with low-fat intake may result from increased production of VLDL TAG, which would explain the increased TAG content and the higher TAG/CE ratio of VLDL from animals fed the low-fat/starch diet.     

Ozone in the Laundry Industry—Practical Experiences in the United Kingdom

Since the early 1990s, the use of ozone in many commercial and industrial laundering applications has been evolving rapidly. Ozone allows washing to be conducted using cold water, thereby saving considerable heat energy and water consumption. Additionally, ozone enhances the wash process, resulting in a significant reduction in detergent dosage and number of rinses, thus saving water. Ozone/cold water cycles are gentler to fabrics, thus extending linen life. Finally, ozone/cold water laundering is beneficial for effluents, resulting in reductions in COD (chemical oxygen demand). Microorganisms are destroyed effectively in ozone-wash waters, and washing and drying cycles are shorter, thus saving labor. In this paper, the authors describe some specific case studies at commercial laundering installations in the UK, whereby the users of ozone have reaped major benefits, including enhanced microorganism kills/inactivation and significant cost savings.     

Fabrication of suspended carbon microstructures by e-beam writer and pyrolysis

A fabrication process has been developed to create suspended carbon microelectromechanical system (C-MEMS) structures. SU-8, a negative photoresist, was used as the starting material and was converted to the desired carbon microstructures using pyrolysis in an inert atmosphere. Suspended carbon-micro and nano electromechanical system (C-MEMS/NEMS) structures with feature sizes down to 500 nm were fabricated by ultra violet/electron beam (EB) lithography and pyrolysis. The problem of charging of the non-conductive SU-8 surface was solved by partially masking a thin metal layer to prevent the repulsion of negative charged electrons before EB writing. Complex suspended C-MEMS structures, such as bridges and networks have been formed. This fabrication method can accurately and reproducibly produce various suspended C-MEMS structures which have applications in microelectronics and biosensing.     

Kinetic studies of the pyrolysis of sewage sludge by tga and comparison with fluidized beds

The pyrolysis of sewage sludge was examined by thermogravimetric analysis using different heating rates, particle sizes and final temperatures. A semi-empirical model was developed with four global consecutive/competitive reactions to volatile and solid products including also a heat balance. This model was extrapolated to isothermal reactor conditions and compared to experimental data on fluidized bed pyrolysis. Depending on the particle size and reactor temperature, about 90% of the maximum conversion in a fluidized bed takes place under external heat transfer control, the rest under kinetic control. Incomplete conversion occurs at short particle residence times, which were calculated approximately by the model.