Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Modeling of polyethylene, poly(l-lactide), and CNT composites: a dissipative particle dynamics study

Dissipative particle dynamics (DPD), a mesoscopic simulation approach, is used to investigate the effect of volume fraction of polyethylene (PE) and poly(l-lactide) (PLLA) on the structural property of the immiscible PE/PLLA/carbon nanotube in a system. In this work, the interaction parameter in DPD simulation, related to the Flory-Huggins interaction parameter χ, is estimated by the calculation of mixing energy for each pair of components in molecular dynamics simulation. Volume fraction and mixing methods clearly affect the equilibrated structure. Even if the volume fraction is different, micro-structures are similar when the equilibrated structures are different. Unlike the blend system, where no relationship exists between the micro-structure and the equilibrated structure, in the di-block copolymer system, the micro-structure and equilibrated structure have specific relationships

Online assessment of patients' views on hospital performances using Rasch model's KIDMAP diagram

<p>Abstract</p> <p>Background</p> <p>To overcome the drawback of individual item-by-item box plots of disclosure for patient views on healthcare service quality, we propose to inspect interrelationships among items that measure a common entity. A visual diagram on the Internet is developed to provide thorough information for hospitals.</p> <p>Methods</p> <p>We used the Rasch rating scale model to analyze the 2003 English inpatient questionnaire data regarding patient satisfactory perception, which were collected from 169 hospitals, examined model-data fit, and developed a KIDMAP diagram on the Internet depicting the satisfaction level of each hospital and investigating aberrant responses with Z-scores and MNSQ statistics for individual hospitals. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across types of hospitals.</p> <p>Results</p> <p>18 of the 45 items fit to the model's expectations, indicating they jointly defined a common construct and an equal-interval logit scale was achieved. The most difficult aspect for hospitals to earn inpatients' satisfaction were item 29 (staff told you about any medication side effects to watch when going home). No DIF in the 18-item questionnaire was found between types of hospitals, indicating the questionnaire measured the same construct across hospitals. Different types of hospitals obtained different levels of satisfaction. The KIDMAP on the Internet provided more interpretable and visualized message than traditional item-by-item box plots of disclosure.</p> <p>Conclusion</p> <p>After removing misfit items, we find that the 18-item questionnaire measures the same construct across types of hospitals. The KIDMAP on the Internet provides an exemplary comparison in quality of healthcare. Rasch analysis allows intra- and inter-hospital performances to be compared easily and reliably with each other on the Internet.</p

Refrigerant- Lubricant Mixture Properties Influencing Bubble Dynamic Parameters and Heat Transfer Coefficient in Nucleate Pool Boiling

We have been successfully developed a model regarding lubricant effect on individual processes of bubble nucleation, growth and departure period for nucleate pool boiling heat transfer. In this study, three type POE refrigeration lubricants with different refrigerant miscibility (POEA/POEB/POEC), two viscosity grades (ISO68 & 170), three kind of refrigerants (R-134a/R-1234ze/R-134yf), and three different saturated temperatures (10℃/0℃/10℃) are taken into calculation under different heat flux ranging from 10 KW/m2 to 80 KW/m2. Based on this model, a knowledge of chemical structures and physical properties of lubricant and refrigerant is sufficient to get bubble dynamic parameters and predict the boiling performance near metal surface. According to calculating results, several key factors play an important role in pool boiling heat transfer and show drastic influence on bubble parameters and HTC, such as refrigerant type, saturated temperature, heat flux and lubricant concentration. Regarding lubricant chemical structure effect on heat transfer performance, it will be direct related to OCR and following influence on HTC in real evaporator environment. But if keeping same lubricant concentration, different results will appear. Various lubricant structures may provide different volume size, adsorption energy on metal surface and interaction force between refrigerant and lubricant, but these factors sometimes offset each other and lead to only a slight difference in bubble size, contact angle, surface coverage concentration, and HTC. The calculation indicates that the presence of lubricant imposes a negative effect on HTC during waiting period of bubble formation and departure period, but a positive effect on HTC may prevail in bubble growth period. Such two effects compete during the boiling process and could lead increase or impair heat transfer performance at a low lubricant concentration

KINETIC ANALYSIS OF LOWER EXTREMITY DURING SIDESTEP CUITING UNDER DIFFERENT DIRECTIONS

The purpose of this study was to investigate the ground reaction forces, joint reaction forces, net muscle joint moments of the ankle, knee and hip during elite lhandball athletes executed typical cutting maneuver under four different directions. Four male elite handball players were tested during fast running (4.5-5.5 m/s) and then performed cutting to the right off (30°, 400 50°, 600 A JVC camera (60 Hz) and synchronized with force plate (1200 Hz) were used to collect the relative parameters of braking leg during cutting maneuver. Each participant's braking leg (right leg) was modeled as a system of rigid bodies. The inverse dynamics approach was used to integrate the body segment parameter, kinetic and force plate data, and to solve the resultant joint moments. The results showed that sidestep cutting maneuver would produce a load and according to the increase of cutting angles, the lower extremity could receive a strike force and moment during the braking phase. Besides, while the knee angle of f1exion was small and repeated loading of this magnitude were enough to produce the fatigue of lower extremity joints that would eventually resu'lt in complete disruption and clinical lower extremity joints injury