Near-field thermomechanical response of a waste vault

The near-field thermomechanical response of an immobilized waste disposal vault in crystalline hard rock was numerically studied taking into account the nonlinear behaviour of the host rock. The results of analyses indicate that the temperature dependence of rock properties has relatively little effect on the transient temperature distributions but may increase the thermal stresses and displacements substantially. However, no deep-seated major overstressed zones are expected.     

Simulation evaluation of Gibbs prior distributions for use in maximum a posteriori SPECT reconstructions

The effects of several of Gibbs prior distributions in terms of noise characteristics, edge sharpness, and overall quantitative accuracy of the final estimates obtained from an iterative maximum a posteriori (MAP) procedure applied to data from a realistic chest phantom are demonstrated. The effects of the adjustable parameters built into the prior distribution on these properties are examined. It is found that these parameter values influence the noise and edge characteristics of the final estimate and can generate reconstructions closer to the actual solution than maximum likelihood (ML). In addition, it is found that the choice of the shape of the prior distribution affects the noise characteristics and edge sharpness in the final estimate.     

Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells

Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM.     

Crystallization behavior of polylactide matrix under the influence of nano‐magnetite

Iron oxide nanoparticle (Fe₃O₄) has gained remarkable research interest for various applications, from environmental to biological, because of its superparamagnetic properties and good biocompatibility. In this work, the nucleation effect of Fe₃O₄ in a polylactide (PLA) matrix under an influence of an alternating magnetic field was studied. The nanocomposite films that is, containing different concentrations of Fe₃O₄ (~8 nm) which were uniformly dispersed in the PLA matrix, were prepared via a solution casting method. The amplitude and frequency of the magnetic field impose great effects on the morphology and nucleation rate of PLA crystallization. Thermogravimetric analysis was used to study the thermal stability of Fe₃O₄/PLA and it showed that the thermal stability of Fe₃O₄/PLA was affected by the Fe₃O₄ content. Fourier transform infrared spectroscopy and X‐ray diffractometry indicated that Fe₃O₄ shows impeding effect to the crystallization of PLA. Based on the differential scanning calorimetry results, composite with 1% of Fe₃O₄ content could promote the crystallization of PLA but it would become an obstacle when 3% of Fe₃O₄ was added. The result of polarized optical microscopy also showed a good agreement that the incorporation of Fe₃O₄ could act as an effective nucleation regent to the composite film. POLYM. ENG. SCI., 59:608–615, 2019. © 2018 Society of Plastics Engineers     

Evaluating p97 Inhibitor Analogues for Potency against p97–p37 and p97–Npl4–Ufd1 Complexes

We previously found that the p97 cofactor, p47, significantly decreased the potency of some ATP‐competitive p97 inhibitors such as ML240 [2‐(2‐amino‐1H‐benzo[d]imidazol‐1‐yl)‐N‐benzyl‐8‐methoxyquinazolin‐4‐amine] and ML241 [2‐(2H‐benzo[b][1,4]oxazin‐4(3H)‐yl)‐N‐benzyl‐5,6,7,8 tetrahydroquinazolin‐4‐amine]. In this study, we aimed to evaluate inhibitor potencies against two additional p97 cofactor complexes, p97–p37 and p97–Npl4–Ufd1. We focused on these two cofactor complexes, because the protein sequence of p37 is 50 % identical to that of p47, and the Npl4–Ufd1 heterodimer (NU) is the most‐studied p97 cofactor complex. We screened 200 p97 inhibitor analogues for their ability to inhibit the ATPase activity of p97 alone and of p97–p37 and p97–NU complexes. In contrast to the effect of p47, p37 and NU did not significantly change the potencies of most of the compounds. These results highlight differences among p97 cofactors in influencing p97 conformation and effects of inhibitors on p97 complexes, as compared to p97 alone. Continued efforts are needed to advance the development of complex‐specific p97 inhibitors.     

Optimization strategy for encapsulation efficiency and size of drug loaded silica xerogel/polymer core‐shell composite nanoparticles prepared by gelation‐emulsion method

It has been commonly discovered that reducing particle size always accompanies with undesirable deterioration of drug encapsulation efficiency in double emulsion based techniques. However, a clear optimization strategy for process variables to minimize this negative impact has been rarely reported. To fill this gap, we have successfully developed an optimization strategy for silica xerogel/polymer composite nanoparticles prepared by our recently developed gelation‐emulsion method. To develop this strategy, interactive effects of multiple process variables were investigated through a four‐factor three‐level experimental design by considering all screened dominant process variables influencing particle size and encapsulation efficiency, including sonication time of second emulsion (t₂), sonication power of the second emulsion (P₂), total volume of the second emulsion (V₂) and volume ratio of aqueous phase and primary emulsion (r). The optimization strategy for fabricating the target particle size with optimal encapsulation efficiency was designed by adjusting the process variables in the order of r, V₂, t₂, and P₂ With this strategy, conspicuous enhancement of the encapsulation efficiency (e.g., from 27 to 63% for a particle size of 211 nm) and significant increment of the feasible size range through our novel fabrication method from 192–569 nm to 90–914 nm have been achieved in this study. POLYM. ENG. SCI., 2017. © 2017 Society of Plastics Engineers     

Influence of microstructure and phase composition on the nanoindentation characterization of bioceramic materials based on hydroxyapatite

The aim of the study was to investigate the influence of microstructure and phase composition on the mechanical behaviour of hydroxyapatite (HAp) and biphasic HAp/β-tricalcium phosphate (β-TCP) bioceramic materials using nanoindentation. The formation of β-TCP phase in the HAp ceramic had the predominant influence on the nanomechanical properties of compact ceramics. For investigated microstructures there appear to be a slight decrease in the elastic modulus with increasing load and a higher decrease in hardness, which are in agreement with upper bounds of the results reported in literature. Maximal value of reduced modulus and hardness is yielded with pure HAp, and is measured to be 133.76 GPa for average grain size of 3 μm and 12.18 GPa for average grain size of 140 nm, respectively. The average modulus and hardness results for HAp/β-TCP ceramics with higher (101.61 GPa, 6.76 GPa) and lower grain size (115.72 GPa, 8.76 GPa) show sufficient mechanical properties in order to serve as hard tissue replacement material.     

Neuronal spike activity in the nucleus accumbens of behaving rats during ethanol self-administration

Many lines of evidence support the importance of the nucleus accumbens (NAC) for ethanol-reinforced behavior. The nature of the neuronal activity that occurs in this region during ethanol self-administration is not known. We recorded from ensembles of single-units primarily located within the shell of the NAC during operant responding for oral ethanol solutions by well-trained rats. Of 90 units recorded from seven sessions from seven rats, 41 (46%) did not exhibit significant changes in relation to the experimental events. Of the 49 units (54%) that did exhibit significant phasic changes, alterations in firing rate occurred in relation to the following experimental events: operant response (63%), tone stimulus (20%), and ethanol delivery (63%). In addition, changes in spike activity during the intervals between the three experimental events were noted in 33% of the units. Most units (55% of responsive units) responded to multiple experimental events. Thus different but overlapping populations of neurons in the NAC represent each event that occurs along the temporal dimension of a single trial performed to obtain ethanol reward. The data suggest that the NAC plays a crucial role in linking together conditioned and unconditioned internal and external stimuli with motor plans to allow for ethanol-seeking behavior to occur.