Influence mechanism of polycrystalline diamond compact bit temperature rise based on thermo-fluid-solid coupling.

In order to improve the drilling performance of polycrystalline diamond compact bit and prolong its service life during drilling in coal rock under the action of wind cycle, the theoretical calculation model of polycrystalline diamond compact bit cutting teeth temperature was derived based on the theory of tribology and heat transfer. The theoretical temperature field of polycrystalline diamond compact bit-cutting teeth was analyzed. Using the joint simulation of EDEM-FLUENT, the temperature variation law of polycrystalline diamond compact bit cutting teeth under the thermo-fluid-solid coupling was analyzed to verify the validity of the theoretical calculation model of polycrystalline diamond compact bit cutting teeth temperature. By building a rotary drilling test platform and conducting drilling experiments on polycrystalline diamond compact bit under different drilling parameters respectively, the correctness of the theoretical model and the simulation data were verified. In addition, a response surface analysis model was established to study the influence of different drilling parameters on the polycrystalline diamond compact bit cutting teeth temperature during drilling in coal rock. The analysis results show that the influence degree of various drilling parameters on the polycrystalline diamond compact bit cutting teeth temperature from large to small is drilling pressure, drilling speed, coal rock properties, and wind speed. Compared with the working condition without wind cycle, the drilling efficiency of polycrystalline diamond compact bit can be increased by 14.38% and the temperature is reduced by 8% when it drills in coal. The drilling efficiency of polycrystalline diamond compact bit can be increased by 17.79% and the temperature is reduced by 10.5% when it drills in coal gangue.

Pretreatment serum albumin-to-alkaline phosphatase ratio is an independent prognosticator of survival in patients with metastatic gastric cancer.

BACKGROUND: Previous studies have suggested that a low albumin-to-alkaline phosphatase ratio (AAPR) is associated with a lower survival rate in patients with various malignancies. However, the relationship between pretreatment AAPR and the prognosis of patients with gastric cancer (GC) remains unclear. AIM: To investigate the prognostic value of AAPR in distant metastatic GC. METHODS: A total of 191 patients with distant metastatic cancer from a single institute were enrolled in this study. Pretreatment clinical data, including serum albumin and alkaline phosphatase levels, were collected. A chi-square test or Fisher's exact test was applied to evaluate the correlations between AAPR and various clinical parameters in GC patients. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic efficacy of AAPR in metastatic GC patients. A two-sided P value lower than 0.05 was considered statistically significant. RESULTS: A receiver operating characteristic curve indicated that 0.48 was the optimal threshold value for AAPR. AAPR ≤ 0.48 was significantly associated with bone (P < 0.05) and liver metastasis (P < 0.05). Patients with high levels of AAPR had better survival in terms of overall survival (OS) and progression-free survival (PFS), regardless of the presence of liver/bone metastasis. Pretreatment AAPR was found to be a favorable predictor of OS and PFS based on a multivariate cox regression model. AAPR-M system, constructed based on AAPR and number of metastatic sites, showed superior predictive ability relative to the number of metastatic sites for predicting survival. CONCLUSION: Pretreatment AAPR may serve as an independent prognostic factor for predicting PFS and OS in patients with metastatic GC. Furthermore, AAPR may assist clinicians with individualizing treatment.

Stick-slip vibration characteristics of drilling tool during drilling in coal seam with gangue.

Aiming at the problem of stick-slip vibration caused by sudden drilling resistance torque during drilling in coal seam with gangue, the drilling tool dynamic model with two degree of freedom was established based on the interaction between the bit cutting teeth and the coal seam with gangue. So, the motion differential equation of torsional vibration of drilling tool was derived, and the torsional vibration response of drilling tool was analyzed. Taking the drilling tool with drilling depth of 300 m as an example, the response laws of angular displacement, angular velocity, resistance torque, driving torque, relative motion phase trajectory and torsional vibration of the drill bit were discussed. The results show that the drilling tool has obvious stick-slip vibration under the action of sudden drilling resistance in the process of drilling in coal seam with gangue. The angular velocity of the drill bit moves alternately between the viscous stage and the sliding stage. A stable limit cycle will appear in the phase trajectory curve of the drill bit.

Tribological Behavior of Phenolic Resin-Based Friction Composites Filled with Graphite.

In this paper, the influence of graphite (Gr) on the dry sliding tribological properties of phenolic resin (PF) composites was studied under different sliding speeds of 3.1-47.1 m/s. The wear mechanism was investigated by the observation of the morphology of the transfer layer during the dry sliding process. It was found that the addition of Gr could decrease the friction coefficient and wear rate effectively, and the friction coefficient and wear rate decreased with the increase of Gr content in the range of 10-30 vol.%. The dominant wear mechanisms of PF-based friction composites changed from adhesive wear to fatigue wear (in the form of peeling-off) in the high sliding speed condition after the addition of Gr. The addition of Gr effectively reduced the sensitivity of PF-based friction materials to sliding speeds, and thus enhanced the stability of the friction coefficient. When the content of Gr was above 20 vol.%, the stability of the friction coefficient was relatively steady.

Comparison of Multiple Displacement Amplification (MDA) and Multiple Annealing and Looping-Based Amplification Cycles (MALBAC) in Limited DNA Sequencing Based on Tube and Droplet.

Whole genome amplification (WGA) is crucial for whole genome sequencing to investigate complex genomic alteration at the single-cell or even single-molecule level. Multiple displacement amplification (MDA) and multiple annealing and looping based amplification cycles (MALBAC) are two most widely applied WGA methods, which have different advantages and disadvantages, dependent on research objectives. Herein, we compared the MDA and MALBAC to provide more information on their performance in droplets and tubes. We observed that the droplet method could dramatically reduce the amplification bias and retain the high accuracy of replication than the conventional tube method. Furthermore, the droplet method exhibited higher efficiency and sensitivity for both homozygous and heterozygous single nucleotide variants (SNVs) at the low sequencing depth. In addition, we also found that MALBAC offered a greater uniformity and reproducibility and MDA showed a better efficiency of genomic coverage and SNV detection. Our results provided insights that will allow future decision making.

Pressure drop characteristics of reverse circulation pneumatic cuttings removal during coal seam drilling.

To solve the problems that the borehole depth is shallow and the drilling efficiency is low during the gas drainage drilling in soft coal seam with current cuttings removal method, a new technology of reverse circulation pneumatic cuttings removal is proposed. The working principle of reverse circulation pneumatic cuttings removal is analyzed, and the kinetic equation of cuttings in the inner hole of the drill pipe is established. Through experiments, the pressure drop in the drill pipe is measured to reveal the effects of air velocity, cuttings mass flow rate, and cuttings particle size on the pressure drop in inner hole of the drill pipe. When the cuttings mass flow rate is constant, the pressure drop increases with the increase in air velocity. When the air velocity is constant, the pressure drop increases with the increase in cuttings mass flow rate. At low air velocity, the pressure drop of cuttings is primary. As the air velocity increases, the pressure drop ratio of cuttings decreases. Under the same conditions, the order of pressure drop with different particle size cuttings is coarse cuttings > medium cuttings > fine cuttings. Empirical equation of pressure drop coefficient of cuttings is established, which is in good agreement with the actual data.

Continuous Microfluidic Purification of DNA Using Magnetophoresis.

Automatic microfluidic purification of nucleic acid is predictable to reduce the input of original samples and improve the throughput of library preparation for sequencing. Here, we propose a novel microfluidic system using an external NdFeB magnet to isolate DNA from the polymerase chain reaction (PCR) mixture. The DNA was purified and isolated when the DNA-carrying beads transported to the interface of multi-laminar flow under the influence of magnetic field. Prior to the DNA recovery experiments, COMSOL simulations were carried out to study the relationship between trajectory of beads and magnet positions as well as fluid velocities. Afterwards, the experiments to study the influence of varying velocities and input of samples on the DNA recovery were conducted. Compared to experimental results, the relative error of the final position of beads is less than 10%. The recovery efficiency decreases with increase of input or fluid velocity, and the maximum DNA recovery efficiency is 98.4% with input of l00 ng DNA at fluid velocity of 1.373 mm/s. The results show that simulations significantly reduce the time for parameter adjustment in experiments. In addition, this platform uses a basic two-layer chip to realize automatic DNA isolation without any other liquid switch value or magnet controller.

Development of Body Mass Index Growth Standard Chart for Chinese Preschool Children.

BACKGROUND: We aimed to establish a reference standard of Body Mass Index (BMI) for the growth of preschool children in China. METHODS: We monitored and obtained the height and weight of 50702 children aged 3-6 yr in 31 provinces in mainland China in 2014. The reference standard and percentile curve of BMI preschool children aged 3-6 yr old were formulated by using Lambda-Median-Sigma (LMS) method in China. RESULTS: The common grounds of the male and female children were as follows: the percentile maps were similar in shape; the graphs of children aged 4-6 were approximately horn shaped. The differences between male and female children were as follows: the BMI values of male children in the same age group and the same percentile were higher than those of the female children. The change pattern of male children was larger than that of female children. BMI of 3 yr old and 6 yr old children was larger than those of 4 yr old and 5 yr old. During the change from low percentile to high percentile, the BMI values of Chinese male children exceeded WHO to a larger extent, and the BMI values of Chinese female children were substantially consistent with WHO, but the high percentile greater than P95 exceeded WHO. CONCLUSION: The BMI growth chart developed can be applied in monitoring the growth and nutrition of preschool children in China. We recommend the promotion of the results in the field of preventive health care.

Computation of Propagating and Non-Propagating Lamb-Like Wave in a Functionally Graded Piezoelectric Spherical Curved Plate by an Orthogonal Function Technique.

Non-propagating waves have great potential for crack evaluation, but it is difficult to obtain the complex solutions of the transcendental dispersion equation corresponding to the non-propagating wave. This paper presents an analytical approach based on the orthogonal function technique to investigate non-propagating Lamb-like waves in a functionally graded piezoelectric spherical curved plate. The presented approach can transform the set of partial differential equations for the acoustic waves into an eigenvalue problem that can give the generally complex wave numbers and the field profiles. A comparison of the obtained results with the well-known ones in plates is provided. The obtained solutions of the dispersion equation are shown graphically in three dimensional frequency-complex wave number space, which aids in understanding the properties of non-propagating waves better. The properties of the guided wave, including real, purely imaginary, and complex branches in various functionally graded piezoelectric spherical curved plates, are studied. The effects of material piezoelectricity, graded fields, and mechanical and electrical boundary conditions on the dispersion characteristics, are illustrated. The amplitude distributions of displacement and electric potential are also discussed, to analyze the specificities of non-propagating waves.

Cyclin-dependent kinase 5 controls vasculogenic mimicry formation in non-small cell lung cancer via the FAK-AKT signaling pathway.

Vasculogenic mimicry (VM), an endothelial-independent tumor vascularization phenomenon representing functional tumor plasticity, might be the culprit behind the poor clinical outcome in classic antiangiogenesis treatment. However, the mechanism underlying VM needs to be elucidated. Cyclin-dependent kinase 5 (CDK5) has been recognized as a key factor in regulating migration and neuronal plasticity. Recently, CDK5 was associated with tumor migration and invasion and its expression levels correlated with poor clinical prognosis, indicating its important role in tumor cell plasticity. In this study, we determined the presence of VM network in the lung cancer cell line A549 by tube formation assay. Selective inhibition of CDK5 expression by roscovitine or siRNA significantly decreased VM formation in A549 cells both in vitro and in vivo and retarded tumor growth. To investigate the possible mechanism, we detected the downstream pathway of CDK5 by Western blotting and immunohistochemistry. We found that CDK5 silencing led to significant decrease in FAKSer732 and AKTSer472 phosphorylation level. Further studies showed that FAK knockdown impaired VM formation and deregulated cytoskeleton transformation of A549 cells. And these effects caused by FAK silence couldn't be reversed by adding CDK5 recombinant protein. This study indicates that CDK5 kinase activates the FAK/AKT signaling pathway to generate VM in a lung cancer cell line, which can help us develop potential therapeutic strategies against vessel-positive tumors.

Impacts of the charged residues mutation S48E/N62H on the thermostability and unfolding behavior of cold shock protein: insights from molecular dynamics simulation with Go model.

The cold shock protein from the hyperthermophile Thermotoga maritima (Tm-Csp) exhibits significantly higher thermostability than its homologue from the thermophile Bacillus caldolyticus (Bc-Csp). Experimental studies have shown that the electrostatic interactions unique to Tm-Csp are responsible for improving its thermostability. In the present work, the favorable charged residues in Tm-Csp were grafted into Bc-Csp by a double point mutation of S48E/N62H, and the impacts of the mutation on the thermostability and unfolding/folding behavior of Bc-Csp were then investigated by using a modified Go model, in which the electrostatic interactions between charged residues were considered in the model. Our simulation results show that this Tm-Csp-like charged residue mutation can effectively improve the thermostability of Bc-Csp without changing its two-state folding mechanism. Besides that, we also studied the unfolding kinetics and unfolding/folding pathway of the wild-type Bc-Csp and its mutant. It is found that this charged residue mutation obviously enhanced the stability of the C-terminal region of Bc-Csp, which decreases the unfolding rate and changes the unfolding/folding pathway of the protein. Our studies indicate that the thermostability, unfolding kinetics and unfolding/folding pathway of Bc-Csp can be artificially changed by introducing Tm-Csp-like favorable electrostatic interactions into Bc-Csp.

The Intrinsic Dynamics and Unfolding Process of an Antibody Fab Fragment Revealed by Elastic Network Model.

Antibodies have been increasingly used as pharmaceuticals in clinical treatment. Thermal stability and unfolding process are important properties that must be considered in antibody design. In this paper, the structure-encoded dynamical properties and the unfolding process of the Fab fragment of the phosphocholine-binding antibody McPC603 are investigated by use of the normal mode analysis of Gaussian network model (GNM). Firstly, the temperature factors for the residues of the protein were calculated with GNM and then compared with the experimental measurements. A good result was obtained, which provides the validity for the use of GNM to study the dynamical properties of the protein. Then, with this approach, the mean-square fluctuation (MSF) of the residues, as well as the MSF in the internal distance (MSFID) between all pairwise residues, was calculated to investigate the mobility and flexibility of the protein, respectively. It is found that the mobility and flexibility of the constant regions are higher than those of the variable regions, and the six complementarity-determining regions (CDRs) in the variable regions also exhibit relative large mobility and flexibility. The large amplitude motions of the CDRs are considered to be associated with the immune function of the antibody. In addition, the unfolding process of the protein was simulated by iterative use of the GNM. In our method, only the topology of protein native structure is taken into account, and the protein unfolding process is simulated through breaking the native contacts one by one according to the MSFID values between the residues. It is found that the flexible regions tend to unfold earlier. The sequence of the unfolding events obtained by our method is consistent with the hydrogen-deuterium exchange experimental results. Our studies imply that the unfolding behavior of the Fab fragment of antibody McPc603 is largely determined by the intrinsic dynamics of the protein.

[Correction of electrocardiogram signal baseline wander based on statistically weighted moving average filter].

Baseline wander (BW) is a common noise contaminating electrocardiogram (ECG). In order to effectively correct baseline of ECG signal and to preserve more latent components of ECG signal, this paper proposes a simple and novel filter based on statistically weighted moving average. Firstly, after the arrange between the maximum and the minimum of these sampling values in a moving window was divided into many sections with equal width, several segments [a(k), b(k)] including most samples were determined. Then, for every sample point in the moving window its weight was decided according to the criterion: its weight was set as 1 if the sampling value belongs to [a(k), b(k)], otherwise, as 0. Lastly, all these ECG sampling points with 1 weight were averaged to estimate the real baseline in the moving window. The algorithm was tested by simulated signal and real signal from www. physionet. org. The results showed that compared to traditional moving average filter and wavelet package (WP) translation, the proposed filter could more effectively correct baseline in ECG signal and result in less distortion to ECG signal.

Optimization of peptide density on microarray surface for quantitative phosphoproteomics.

Procedures to determine the density of peptides immobilized on a glass surface for the quantitative detection of phosphorylated peptides for phosphoproteomic applications of peptide microarrays are described. Two kinds of representative fluorescent probe molecules, anti-phosphotyrosine antibody (AB) and phos-tag (PT), were examined to compare their ability for the quantitative detection of phosphorylated peptides. PT is a metal complex with a binding specificity to phosphorylated amino acids, and is much smaller in size than AB. Thus, PT is quantitatively bound to the phosphorylated peptides, even at a high immobilization density without steric hindrance, making them highly suited for future microarrays requiring smaller sized peptide spots for much higher throughput.

A peptide microarray for detecting protein kinase activity in cell lysates.

Protein kinases (PKs) are widely recognized as valuable targets for disease diagnosis and drug discovery. For this reason, we have developed a sensitive peptide microarray for detecting intracellular PK activity. Peptides are immobilized on a glutaraldehyde-premodified high-amino terminal glass slide, by spotting 2 nL volumes of substrate peptide solutions with an automated microarray spotter. After the peptides are phosphorylated by cell lysates, phosphorylation is specifically recognized by a fluorescence-labeled antiphosphotyrosine antibody for tyrosine kinases, or Phos-tag biotin (a biotinylated phosphate-specific ligand based on Zn(2+) complex), which is subsequently bound with fluorescence-labeled streptavidin, for serine/threonine kinases. The fluorescence signal is then detected by an automatic microarray scanner. The peptide microarray system involves simple peptide immobilization, requires low sample volumes and provides a high density array. Importantly, it provides high sensitivity for detecting PK activities in cell lysates. Thus, the peptide microarray system is expected to be useful for a high-throughput kinase assay to investigate intracellular kinase activity and has potential applications in disease diagnosis and drug discovery.

Protein kinase substrate profiling with a high-density peptide microarray.

We describe a powerful peptide microarray for profiling protein kinase substrates that combines the merits of chemoselective immobilization of peptides to achieve high density spots with the advantages of fluorescence-based analysis of phosphorylation for nonhazardous detection. For detection of on-chip phosphorylation, we used a fluorescence-labeled antiphosphotyrosine antibody to detect phosphotyrosine and a biotinylated Phostag, which was subsequently bound with a fluorescence-labeled streptavidin for phosphoserine/threonine. More than 290 kinds of Tyr peptides and over 1,100 kinds of Ser/Thr peptides were chemoselectively immobilized onto a glass surface in a high-density format to profile a panel of protein kinases, including c-Src, c-Abl, EGFR, JNK1, ERK2, p38α, and PKA. Many novel, highly reactive and specific peptides were identified as substrates for each protein kinase. Most substrates had the consensus motifs that have been reported previously but some new motifs were also found. The identification of two designed peptides that have higher reactivity than the famous PKA substrate (Kemptide) indicates that analysis of the amino acid biases of substrates is very helpful to the design of new substrates with high reactivity. Thus, the high-density peptide microarray is expected to be a powerful approach for high-throughput discovery of potential substrates for protein kinases.

[Arithmetic for subtracting power line interference based on estimating sinusoidal parameters].

Electrocardiogram (ECG) signals are often contaminated by residual power-line interference. In order to filter the noise and not to distort signal too much, certain types of digital notch filters need a narrow frequency band, but such a band leads to ineffective filtering in the case of frequency deviation of the interference. In this paper, we propose a novel arithmetic. Firstly, sinusoidal parameters (frequency and phase) are estimated from the sinusoidal values in the linear segment of ECG. Secondly, a sinusoid function in linear segment is determined by the estimated sinusoidal parameters. Thirdly, the interference values in the nonlinear segment closest to the linear segment are calculated by the sinusoid function. Lastly, we subtract the corresponding interference value from the real value. The experiment results show that, in comparison with other arithmetic, the novel arithmetic can more effectively remove the power-line interference from ECG signal.

Monitoring protein kinase activity in cell lysates using a high-density peptide microarray.

Monitoring and targeting protein kinases is widely accepted as a promising approach for disease diagnosis and drug discovery. For this purpose, the authors have developed an original type of peptide array as a high-throughput screening assay for quantitatively evaluating kinase activity. A volume of 2 nL of peptide solution was spotted onto a formyl group-modified glass slide by using an arrayer, which was designed for use with protein chip technology. The phosphorylation was recognized by fluorescence-label antibody and detected with an automatic microarray scanner widely used in DNA chip technology. The system needs low sample volume, provides a high-density peptide array, and supplies high reproducibility. It provided enough sensitivity for inhibitor screening, even though a relatively low concentration of purified kinase was employed. The assay also proved useful for the detection of intracellular kinase activity as well as for the measurement of the fluctuations of intracellular protein kinase activity with drug stimulation. Thus, this peptide array would be applicable for kinase-targeted diagnosis, cell-based drug screening, and signal pathway investigation.

Transplantation of sertoli-islet cell aggregates formed by microgravity: prolonged survival in diabetic rats.

Transplantation of pancreatic islets is a potentially attractive treatment for type I diabetes. We generated the transplantable, tissue-like aggregates composed of Sertoli cells and islets in rotating wall vessel bioreactors, SICA (Sertoli-islet cell aggregates), to improve their biological function in vitro and in vivo. The isolated islet equivalent and Sertoli cells were purified from Wistar rats and cocultured for 5 days in bioreactor to generate SICA. The SICA, islets aggregates, and fresh isolated islets were transplanted under the kidney capsule of diabetic Sprague-Dawley (SD) rats, respectively. The functions of different grafts were ascertained by blood glucose level measurements and an in vivo glucose tolerance test. In response to elevated glucose, insulin secretion from SICA was 1.4-fold higher (P<0.05, n=5) than islet aggregates cultured alone. Of the rats that received SICA, 90% (9/10) remained normoglycemic at 60 days post-transplantation, and the survival significantly increased compared with recipients bearing homotypic islets aggregates or freshly isolated islets. The former responded similarly with healthy rats to the glucose tolerance test. Our results support the usefulness of SICA for the treatment of type 1 diabetes without any immunosuppressive agents.