Parametric optimization and heat transfer analysis of a dual loop ORC (organic Rankine cycle) system for CNG engine waste heat recovery

In this study, a dual loop ORC (organic Rankine cycle) system is adopted to recover exhaust energy, waste heat from the coolant system, and intercooler heat rejection of a six-cylinder CNG (compressed natural gas) engine. The thermodynamic, heat transfer, and optimization models for the dual loop ORC system are established. On the basis of the waste heat characteristics of the CNG engine over the whole operating range, a GA (genetic algorithm) is used to solve the Pareto solution for the thermodynamic and heat transfer performances to maximize net power output and minimize heat transfer area. Combined with optimization results, the optimal parameter regions of the dual loop ORC system are determined under various operating conditions. Then, the variation in the heat transfer area with the operating conditions of the CNG engine is analyzed. The results show that the optimal evaporation pressure and superheat degree of the HT (high temperature) cycle are mainly influenced by the operating conditions of the CNG engine. The optimal evaporation pressure and superheat degree of the HT cycle over the whole operating range are within 2.5–2.9 MPa and 0.43–12.35 K, respectively. The optimal condensation temperature of the HT cycle, evaporation and condensation temperatures of the LT (low temperature) cycle, and exhaust temperature at the outlet of evaporator 1 are kept nearly constant under various operating conditions of the CNG engine. The thermal efficiency of the dual loop ORC system is within the range of 8.79%–10.17%. The dual loop ORC system achieves the maximum net power output of 23.62 kW under the engine rated condition. In addition, the operating conditions of the CNG engine and the operating parameters of the dual loop ORC system significantly influence the heat transfer areas for each heat exchanger

Measurement method and model simulation of the benchmark line in the deformed frame of a heavy vehicle

Wheel alignment is an important item of vehicle detection to ensure the vehicle safety. The precision of wheel alignment is determined by the benchmark line which is the center line of the vehicle frame. A measurement method of the benchmark line for the deformed frame of heavy vehicle is deduced by constructing a model which consists of a laser bar with two laser range finders and a measurement bar with scale. The simulations are performed on a model of typical heavy vehicle CA1190 whose frame size is 11230 mm×860 mm. The simulation results of the center points are solved by the least squares method while the fitting line of the points for the benchmark line is also achieved in the simulation

SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.

BACKGROUND: The Mnk2 kinase, encoded by MKNK2 gene, plays critical roles in MAPK signaling and was involved in oncogenesis. Human MKNK2 pre-mRNA can be alternatively spliced into two splicing isoforms, the MKNK2a and MKNK2b, thus yielding Mnk2a and Mnk2b proteins with different domains. The involvement of Mnk2 alternative splicing in colon cancer has been implicated based on RNA-sequencing data from TCGA database. This study aimed at investigating the upstream modulators and clinical relevance of Mnk2 alternative splicing in colon adenocarcinoma (CAC). METHODS: PCR, western blotting and immunohistochemistry (IHC) were performed to assess the expression of Mnk2 and upstream proteins in CAC. The function of Mnk2 and its regulators were demonstrated in different CAC cell lines as well as in xenograft models. Two independent cohorts of CAC patients were used to reveal the clinical significance of MKNK2 alternative splicing. RESULTS: Comparing with adjacent nontumorous tissue, CAC specimen showed a decreased MKNK2a level and an increased MKNK2b level, which were correlated with KRAS mutation and tumor size. The SRSF1 (serine/arginine-rich splicing factor 1) was further confirmed to be the major splicing factor targeting MKNK2 in CAC cells. Higher expression of SRPK1/2 or decreased activity of PP1α were responsible for enhancing SRSF1 phosphorylation and nucleus translocation, subsequently resulted in a switch of MKNK2 alternative splicing. CONCLUSIONS: Our data showed that phosphorylation and subcellular localization of SRSF1 were balanced by SRPK1/2 and PP1α in CAC cells. High nucleus SRSF1 promoted MKNK2 splicing into MKNK2b instead of MNK2a, consequently enhanced tumor proliferation

Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails

<p>Abstract</p> <p>Background</p> <p>Brd2 is a transcriptional regulator and belongs to BET family, a less characterized novel class of bromodomain-containing proteins. Brd2 contains two tandem bromodomains (BD1 and BD2, 46% sequence identity) in the N-terminus and a conserved motif named ET (extra C-terminal) domain at the C-terminus that is also present in some other bromodomain proteins. The two bromodomains have been shown to bind the acetylated histone H4 and to be responsible for mitotic retention on chromosomes, which is probably a distinctive feature of BET family proteins. Although the crystal structure of Brd2 BD1 is reported, no structure features have been characterized for Brd2 BD2 and its interaction with acetylated histones.</p> <p>Results</p> <p>Here we report the solution structure of human Brd2 BD2 determined by NMR. Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon <it>π</it>-helix, termed <it>π</it>D. The helix <it>π</it>D forms a portion of the acetyl-lysine binding site, which could be a structural characteristic of Brd2 BD2 and other BET bromodomains. Unlike Brd2 BD1, BD2 is monomeric in solution. With NMR perturbation studies, we have mapped the H4-AcK12 peptide binding interface on Brd2 BD2 and shown that the binding was with low affinity (2.9 mM) and in fast exchange. Using NMR and mutational analysis, we identified several residues important for the Brd2 BD2-H4-AcK12 peptide interaction and probed the potential mechanism for the specific recognition of acetylated histone codes by Brd2 BD2.</p> <p>Conclusion</p> <p>Brd2 BD2 is monomeric in solution and dynamically interacts with H4-AcK12. The additional secondary elements in the long ZA loop may be a common characteristic of BET bromodomains. Surrounding the ligand-binding cavity, five aspartate residues form a negatively charged collar that serves as a secondary binding site for H4-AcK12. We suggest that Brd2 BD1 and BD2 may possess distinctive roles and cooperate to regulate Brd2 functions. The structure basis of Brd2 BD2 will help to further characterize the functions of Brd2 and its BET members.</p

Causes of death and conditional survival estimates of long-term lung cancer survivors.

INTRODUCTION: Lung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer. METHODS: We collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients\u27 survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy era, n=42061). RESULTS: Of the 612,100 patients, 285,705 were women, the mean (SD) age was 68.3 (11.0) years old. 252,558 patients were characterized as lung adenocarcinoma, 133,302 cases were lung squamous cell carcinoma, and only 78,700 cases were small cell lung carcinomas. TNM stage was I in 140,518 cases, II in 38,225 cases, III in 159,095 cases, and IV in 274,262 patients. 164,394 cases underwent surgical intervention. The 5-y overall survival and cancer-specific survival were 54.2% and 73.8%, respectively. The 5-y conditional survival rate of cancer-specific survival is improved in a time-dependent pattern, while conditional overall survival tends to be steady after 5-y follow-up. Except from age, hazard disparities of other risk factors (such as stage and surgery) diminished over time according to the conditional survival curves. After 8 years since diagnosis, mortality hazard from other causes became higher than that from lung cancer. This critical time point was earlier in elder patients while was postponed in patients with advanced stages. Moreover, both cancer-specific survival and overall survival of metastatic patients in immunotherapy era were significantly better than those in non-immunotherapy era (P CONCLUSIONS: Our findings expand on previous studies by demonstrating that non-lung-cancer related death risk becomes more and more predominant over the course of follow-up, and we establish a personalized web-based calculator to determine this critical time point for long-term survivors. We also confirmed the survival benefit of advanced lung cancer patients in immunotherapy era

Measurement method and model simulation of the benchmark line in the deformed frame of a heavy vehicle

Wheel alignment is an important item of vehicle detection to ensure the vehicle safety. The precision of wheel alignment is determined by the benchmark line which is the center line of the vehicle frame. A measurement method of the benchmark line for the deformed frame of heavy vehicle is deduced by constructing a model which consists of a laser bar with two laser range finders and a measurement bar with scale. The simulations are performed on a model of typical heavy vehicle CA1190 whose frame size is 11230 mm×860 mm. The simulation results of the center points are solved by the least squares method while the fitting line of the points for the benchmark line is also achieved in the simulation