Growth and properties of CdxHg1−xTe crystals

It has been found that there are two main factors complicating the preparation of Cd_xHg_1–xTe. The marked difference between the liquidus and solidus curves of the CdTe-HgTe pseudo-binary system gives the expected problems of segregation of CdTe with respect to HgTe during growth but there are also problems due to the segregation of any excess Te in the melt. A 2% excess of Te can give rise to pronounced constitutional supercooling effects. To avoid this, careful control of melt stoichiometry is required. This is made difficult by the high vapour pressure of mercury over the melt, the value of which is not known with great accuracy.The conditions of melt stoichiometry required for crystal growth do not necessarily give material of the required type and resistivity and this must be adjusted after growth by annealing at a controlled mercury pressure at a fixed temperature.     

Inhibition of WHSC1 Allows for Reprogramming of the Immune Compartment in Prostate Cancer

Immunotherapy initially demonstrated promising results in prostate cancer (PCa), but the modest or negative results of many recent trials highlight the need to overcome the poor immunogenicity of this cancer. The design of effective therapies for PCa is challenged by the limited understanding of the interface between PCa cells and the immune system in mediating therapeutic resistance. Prompted by our recent observations that elevated WHSC1, a histone methyltransferase known to promote progression of numerous cancers, can silence antigen processing and presentation in PCa, we performed a single-cell analysis of the intratumoral immune dynamics following in vivo pharmacological inhibition of WHSC1 in mice grafted with TRAMP C2 cells. We observed an increase in cytotoxic T and NK cells accumulation and effector function, accompanied by a parallel remodeling of the myeloid compartment, as well as abundant shifts in key ligand–receptor signaling pathways highlighting changes in cell-to-cell communication driven by WHSC1 inhibition. This comprehensive profiling of both immune and molecular changes during the course of WHSC1 blockade deepens our fundamental understanding of how anti-tumor immune responses develop and can be enhanced therapeutically for PCa.     

Effect of orlistat on fat absorption in rats: A comparison of normal rats and rats with diverted bile and pancreatic juice

Orlistat is a specific inhibitor of pancreatic and gastric lipases leading to decreased absorption of fat. In the present study, we measured the effect of orlistat on lymphatic fat transport in rats following intake of oils very different in FA composition and TAG structure, and compared this with the transport in normal rats and rats with fat malabsorption. Rats were subjected to cannulation of the main mesenteric lymph duct, and a feeding catheter was inserted into the stomach. In addition, malabsorbing rats were cannulated in the common bile and pancreatic duct. Emulsified safflower, fish, and randomized oils were administered, and lymph was collected for 24 h and analyzed for FA composition. Administration of 25 mg orlistat together with the dietary oils resulted in very small changes from baseline lymphatic transport, indicating that inhibition of the fat absorption was almost complete and furthermore that the source of fat had no influence on the inhibitory effect of orlistat. Orlistat did not interfere with the absorption of the hydrolysis products, since high absorption of sn-2 MAG and FFA (oleic acid) mixed with orlistat was observed. The baseline lymphatic transport in the orlistat group was higher than in the malabsorbing group, but this was the result of generally lower transport of endogenous FA in the malabsorbing group, presumably caused by the absence of bile FA. The transport of FA in normal rats was several-fold higher than the transport after orlistat addition and in malabsorbing rats. Thus, this study showed that orlistat inhibited fat hydrolysis, and thereby lymphatic absorption, almost completely independently of the fat administered.     

Perfluorocarbons in Chemical Biology

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and ¹⁹F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.     

Designed Multifunctional Nanocomposites for Biomedical Applications

The assembly of multifunctional nanocomposite materials is demonstrated by exploiting the molecular sieving property of SBA‐16 nanoporous silica and using it as a template material. The cages of the pore networks are used to host iron oxide magnetic nanoparticles, leaving a pore volume of 0.29 cm³ g^?1 accessible for drug storage. This iron oxide–silica nanocomposite is then functionalized with amine groups. Finally the outside of the particle is decorated with antibodies. Since the size of many protein molecules, including that of antibodies, is too large to enter the pore system of SBA‐16, the amine groups inside the pores are preserved for drug binding. This is proven using a fluorescent protein, fluorescein‐isothiocyanate‐labeled bovine serum albumin (FITC‐BSA), with the unreacted amine groups inside the pores dyed with rhodamine B isothiocyanate (RITC). The resulting nanocomposite material offers a dual‐targeting drug delivery mechanism, i.e., magnetic and antibody‐targeting, while the functionalization approach is extendable to other applications, e.g., fluorescence–magnetic dual‐imaging diagnosis.     

Generating phenotypical erroneous human behavior to evaluate human–automation interaction using model checking

Breakdowns in complex systems often occur as a result of system elements interacting in unanticipated ways. In systems with human operators, human–automation interaction associated with both normative and erroneous human behavior can contribute to such failures. Model-driven design and analysis techniques provide engineers with formal methods tools and techniques capable of evaluating how human behavior can contribute to system failures. This paper presents a novel method for automatically generating task analytic models encompassing both normative and erroneous human behavior from normative task models. The generated erroneous behavior is capable of replicating Hollnagel's zero-order phenotypes of erroneous action for omissions, jumps, repetitions, and intrusions. Multiple phenotypical acts can occur in sequence, thus allowing for the generation of higher order phenotypes. The task behavior model pattern capable of generating erroneous behavior can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human–automation interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. We present benchmarks related to the size of the statespace and verification time of models to show how the erroneous human behavior generation process scales. We demonstrate the method with a case study: the operation of a radiation therapy machine. A potential problem resulting from a generated erroneous human action is discovered. A design intervention is presented which prevents this problem from occurring. We discuss how our method could be used to evaluate larger applications and recommend future paths of development.