The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.     

Deformation of Alumina/Titanium Carbide Composite at Elevated Temperatures

The deformation behavior of an Al₂O₃/30 wt% TIC composite in uniaxial tension was evaluated under vacuum over the temperature range of 1300° to 1550°C. The Al₂0₃/TiC composite exhibited the maximum elongation of 66% at an initial strain rate of 1.19 X l0^-4 s^-1 at 1550°C. The stress exponent calculated from peak stresses of true stress-true strain curves at 1500^OC was 3.8, which was in good agreement with that obtained by changing the crosshead speed during the tension test. The apparent activation energy at 20 MPa was 853 kJ/mol. In addition the deformation of the Al₂O³/TiC composite in uniaxial tension at elevated temperature was accompanied by cavitation.     

Residual stress versus microstructural effects on the strength and toughness of phase-separated PbO–B2O3–Al2O3 glasses

A few authors have reasonably proposed that liquid–liquid phase-separated (LLPS) glasses could show improved fracture strength, S_f, and toughness, K_Ic, as the second phase could provide a barrier to crack propagation via deflection, bowing, trapping, or bridging. Due to the associated tensile or compressive residual stresses, the second phase could also act as a toughening or a weakening mechanism. In this work, we investigated five glasses of the PbO–B₂O₃–Al₂O₃ system spanning across the miscibility gap: Four of them undergo LLPS—three are binodal (two B₂O₃-rich and one PbO-rich) and one is spinodal—and one does not show LLPS (composition outside the miscibility gap). Their compositions were designed in such a way that the amorphous particles are under compressive residual stresses in some and under tensile residual stresses in others. The following mechanical properties were determined: the Vickers hardness, ball on three balls (B3B) strength, and toughness, K_Ic-SEVNB (single-edge V-notch beam [SEVNB]). The microstructures and compositions were analyzed using scanning electron microscopy with energy-dispersive X-ray spectrometry. The spinodal glass showed, by far, the best mechanical properties. Its K_Ic-SEVNB = 1.6 ± 0.1 MPa m^1/2, which embodies an increase of almost 50% over the B₂O₃-rich binodal composition, and 90% considering the PbO-rich binodal composition. Moreover, its fracture strength, S_f = 166 ± 7 MPa, is one of the highest ones ever reported for an LLPS glass. Fracture analyses evidenced that the spinodal composition exhibited the lowest net stress at the fracture point. Moreover, calculations indicate that the internal residual stress level is the lowest in the spinodal glass. The overall results indicate that the microstructural effect of the spinodal glass is the most significant factor for its superior mechanical properties. This work corroborates the idea that LLPS provides a feasible and stimulating solution to improve the mechanical properties of glasses.     

Evaluation of mixing profiles for a new micromixer design strategy

The relationship between mixing history and reaction performance in microreactors using computational fluid dynamics (CFD) simulations is identified. In the idealized, simplified mixing model, mixing proceeds linearly and only the mixing time determined the reaction performance. However, in the case of realistic models where mixing proceeds unequally, the partial rapid progression of mixing, more than the mixing time, significantly impacts the reaction. The use of the fluid segment size distribution to capture this effect is proposed. The effective Damköhler number derived from the fluid segment size distribution predicted the reaction yield well. To demonstrate the utility of the mixing profile design strategy, we fabricated a novel micromixer with multiple partial rapid mixing zones. This micromixer achieved excellent results both in a CFD simulation and an experiment. © 2015 American Institute of Chemical Engineers AIChE J, 62: 1154–1161, 2016     

Hydrophobic Tagged Dihydrofolate Reductase for Creating Misfolded Glycoprotein Mimetics

In the endoplasmic reticulum (ER), nascent glycoproteins that have not acquired the native conformation are either repaired or sorted for degradation by specific quality‐control systems composed by various proteins. Among them, UDP‐glucose:glycoprotein glucosyltransferase (UGGT) serves as a folding sensor in the ER. However, the molecular mechanism of its recognition remains obscure. This study used pseudo‐misfolded glycoproteins, comprising a modified dihydrofolate reductase with artificial pyrene–cysteine moiety on the protein surface (pDHFR) and Man₉GlcNAc₂‐methotrexate (M9‐MTX). All five M9‐MTX/pDHFR complexes, with a pyrene group at different positions, were found to be good substrates of UGGT, irrespective of the site of pyrene modification. These results suggest UGGT's mode of substrate recognition is fuzzy, thus allowing various glycoproteins to be accommodated in the folding cycle.     

Effect of surface properties of silica nanoparticles on their cytotoxicity and cellular distribution in murine macrophages

In this study, complexes composed of poly-l-tyrosine (pLT) and single-walled carbon nanotubes (SWCNTs) were produced and the dispersibility of the pLT/SWCNT complexes in water by measuring the ζ potential of the complexes and the turbidity of the solution were investigated. It is found that the absolute value of the ζ potential of the pLT/SWCNT complexes is as high as that of SWCNTs modified with double-stranded DNA (dsDNA) and that the complexes remain stably dispersed in the water at least for two weeks. Thermogravimetry analysis (TGA) and visualization of the surface structures of pLT/SWCNT complexes using an atomic force microscope (AFM) were also carried out.     

Immunohistochemical quantitation for extracellular matrix proteins in rats with glomerulonephritis induced by monoclonal anti-Thy-1.1 antibody

During clot retraction, platelets interact with fibrin resulting in marked reduction of clot volume. Altered fibrin structure has been reported to affect clot retraction as measured by serum expression. This study was performed to test whether such altered retraction was the result of increased resistance to network collapse or due to decreased force development by platelets. Altered fibrin structure was documented as variation of fibre mass/length ratios (mu) and shifts in clot elastic modulus. The force developed by platelets during clotting was measured directly. Increasing the fibrinogen concentration led to thinner fibre formation (decreased mu), and a linear increase in gel elastic modulus. Over a fibrinogen concentration range of 100 to 400 mg/dl, force development was minimally affected. Force development and clot elastic modulus increased in a linear fashion with increasing platelet concentration. Increasing the calcium concentration from 5 to 20 mM caused a 160% increase in fibrin fibre size (mu), and a 52% decline in clot modulus. Force developed at 1200 s declined by 17%. At 15 mg/ml, dextran and hydroxyethyl starch (HES) also increased mu, and decreased clot modulus; however, both agents markedly reduced force development. Increasing ionic strength or the addition of IgG decreased mu and increased gel elastic modulus. Force development increased modestly with increased ionic strength, did not change with addition of IgG in saline and declined with addition of IgG in maltose. This study indicates that force development is primarily dependent on platelet function while clot modulus depends on both fibrin structure and platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on dry spinning. I. Fundamental equations

One difficulty in analyzing the state of filament in the dry spinning process is that in the boundary conditions required to solve the equations of mass, momentum and energy which are derived on the consideration of balance with respect to infinitesimally small element are not given a priori. The equations which include these boundary conditions in themselves are derived by considering mass, momentum, and energy balances with respect to the entire cross section of filament. These additional macroscopic equations are simplified to a great extent by assuming the flat velocity profile through the cross section of filament. Besides, in the steady state, these macroscopic equations are modified to give the equations of average solvent content, spinning tension, cross-sectional area, and average temperature. When the spinning conditions are given and the physical constants are measured for a given polymer and solvent system, it becomes possible to calculate the state of filament by solving these microscopic and macroscopic equations simultaneously without resorting to actual spinning.     

Thermal resistance in Speer carbon resistors below 1 K

Temperature dependences of Speer carbon resistors between 30 mK and 4.2 K have been measured. The applied electric power at which the resistance decreases by 1% was measured accurately over the same temperature range. From these data, discussions of the thermal resistance of the resistors are made in detail. Some techniques to measure carbon resistance below 1 K, including the method to remove heat leaks, are described.