Search

Objectives: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. Methods: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. Results: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005–1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979–0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989–0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. Conclusions: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied. [ABSTRACT FROM AUTHOR]

In practical engineering projects, bedrock is often encountered under a compressible soil layer. Compared with the soil layer, the hard bedrock has negligible deformation, so the displacement at the bottom of the soil layer is considered to be zero. In this case, it is difficult to use the Boussinesq solution to accurately calculate the stress and displacement of the soil layer under the action of shallow foundations. In the past, the solution has mostly been approximated by the layer-wise summation method or the finite-element method. So far, there is no analytic method to accurately calculate the stress and displacement of the elastic compressible soil layer. In this paper, an analytic method is proposed to solve the plane strain problem under the action of strip foundations. By using a mapping function to convert a soil layer with a finite thickness into the unit circle in the image plane, the stress boundary conditions at the ground surface and the displacement boundary conditions at the bottom of the soil layer are represented by a combined expression for the boundary values of the two analytic functions. A system of linear equations to find the coefficients of the analytic functions is established using a new power series method, and it is solved using the least-squares method. The stress and displacement at any point in the soil layer can be calculated quickly and efficiently using the derived analytic function. The effects of soil layer thickness on soil layer stress and ground surface settlement are discussed, and the results are compared with those obtained by the finite-element method. [ABSTRACT FROM AUTHOR]

• An analytical solution for a lined circular tunnel at shallow depths is presented. • The interaction between surrounding rock and lining is considered. • A new approach is proposed based on complex variable method. • The mechanical contribution of lining is analyzed quantitatively. In this study, a new approach is presented to determine the stress and displacement field of a shallow buried circular tunnel subject to gravity and arbitrary lateral stress based on the complex variable method. The soil mass and lining are conformally mapped onto two ring regions. A more effective method than the power series method is used to solve the undetermined coefficients of complex potential functions. The interaction mechanism between the lining and the soil mass is fully considered. The boundary conditions along the inner boundary of the lining and the ground surface and the stress and displacement continuity conditions along the excavation line are used in the analytical derivation. In the verification, the stress and displacement distributions obtained in the semi-analytical solution agree with the numerical results and satisfy the boundary and continuity conditions. Using examples, the stress distributions along the inner boundary of the lining and interface are presented to examine the influence of key parameters including the Young's modulus and buried depth. The effect of the lining in reducing stress concentration and restricting tunnel convergence is quantitatively analyzed. [ABSTRACT FROM AUTHOR]

An analytical solution for a non‐circular tunnel excavated in an elastic homogeneous half‐plane is obtained, which considers gravity and different lateral pressure coefficients. The solution is deduced using the complex variable method, mapping the region containing a non‐circular tunnel onto a circular ring. The basic equations for the analytic functions are established using the stress boundary conditions at the ground surface and the edges of the tunnel and the analytical functions are solved by the power series method. In the process of solving, the Fourier series was used. To elaborate the solution process clearly and verify the correctness of the solution, a shallow quasi‐ellipse tunnel was analyzed as a computational example, and the results obtained using the presented analytical method are compared with that obtained by the numerical software ANSYS. [ABSTRACT FROM AUTHOR]

Purpose: Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy. Methods: We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144 mg/m2 and 288 mg/m2 of daunorubicin equivalents for standard- and high-risk patients, respectively). Results: The median initial WBC, platelet count, and fibrinogen were 2.9 × 109/L (range 0.9–158.3 × 109/L), 32 × 109/L (range 4–226 × 109/L), and 160 mg/dL (range 53–549 mg/dL), respectively. High-risk and standard-risk were seen in 20.5% and 79.5% of patients, respectively. Three patients (4.1%) suffered early haemorrhagic death. At the end of induction therapy, 68 (93.2%) patients achieved haematologic complete remission (HCR). At a median follow-up of 91.97 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates for the whole cohort were 95.9 ± 2.3% and 88.7 ± 3.8%, respectively. A comparison of HCR rates and documented instances of toxicity between groups A and B + C showed no significant differences. However, idarubicin significantly reduced the peak WBC count (Z = − 3.292, P = 0.001) and duration of hyperleukocytosis (Z = − 2.827, P = 0.005). Estimated 3-year EFS (91.7 ± 8.0%) and OS (100%) rates for group C were not significantly different from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ2 = 5.515, P = 0.019). Conclusions: Idarubicin (8–10 mg/m2/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated. [ABSTRACT FROM AUTHOR]

This paper proposes a method for solving the stress field of a deep circular tunnel affected by an unsteady temperature field. The tunnel is idealized as an infinite domain problem, and the solution of the unsteady temperature field can be regarded as solving the temperature field in the infinite domain under the first type of boundary conditions. The temperature field distribution inside the tunnel surrounding rock is obtained by the Laplace transform method. On this basis, through the stress condition at the boundary of the tunnel and the zero displacement boundary condition at infinity, the solution equations expressed by the analytic functions are listed, and then the power series method of the complex variable function method is used to obtain the desired analytic functions. From this, the temperature stress field caused by the temperature change can be calculated (the displacement field caused by the temperature change is also derived). By superimposing this stress field upon the surrounding rock stress caused by in situ stress, the total stress field inside the surrounding rock can be obtained. The example shows that when the time t is small and the range of the numerical model is suitably large, the results of the analytical method and the numerical method agree well. This paper also discusses two cases in which the tunnel boundary temperature is greater than and less than the initial temperature of the surrounding rock. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional modification and the most prevalent internal RNA modification in eukaryotic cells. YT521-B homology domain family 2 (YTHDF2) is a member of m6A "readers" and its role in human diseases remains unclear. Accumulating evidence suggests that YTHDF2 is greatly implicated in many aspects of human cancers and non-cancers through various mechanisms. YTHDF2 takes a great part in multiple biological processes, such as migration, invasion, metastasis, proliferation, apoptosis, cell cycle, cell viability, cell adhesion, differentiation and inflammation, in both human cancers and non-cancers. Additionally, YTHDF2 influences various aspects of RNA metabolism, including mRNA decay and pre-ribosomal RNA (pre-rRNA) processing. Moreover, emerging researches indicate that YTHDF2 predicts the prognosis of different cancers. Herein, we focus on concluding YTHDF2-associated mechanisms and potential biological functions in kinds of cancers and non-cancers, and its prospects as a prognostic biomarker. [ABSTRACT FROM AUTHOR]

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status. [ABSTRACT FROM AUTHOR]

An analytic stress solution is presented for a circular tunnel problem in a half plane with a concentrated force acting on any position in the field under gravity. The solution uses the complex variable method and the power series method. The influence of the unbalanced force system on the tunnel boundary is considered. The relationship between two analytic functions is established by using surface stress boundary condition. The analytic functions can be determined from the tunnel stress boundary condition. Based on the principle of superposition, the stresses of the surrounding rock can be calculated by superimposing three partial solutions which are obtained separately. The examples give contour plots of the principal stresses in the surrounding rock, focus on the stress distribution on the ground surface and the tunnel boundary and analyze the effect on the stress distribution of some main parameters. [ABSTRACT FROM AUTHOR]

[Display omitted] • 1T/2H MoSe 2 exhibited high removal capacity (Hg(II): 952.4 mg·g−1; Pb(II) 217.9 mg·g−1) and rapid kinetics. • 1T/2H MoSe 2 selectively removed 99% of Hg(II) and Pb(II) under the coexistence of various cations in practical water environment, the separation factors were greater than 170. • 99.6 % of Hg (II) was removed within 180 min, 99.6 % of Pb(II) was removed within 5 min. • The mechanism was elucidated by experiment and DFT calculation. High-efficiency and selective removal of heavy metal ions from aquatic system is urgently needed and remains a major challenge. Endowed with rich Se atoms and unique 2D structure, MoSe 2 should be promising for the removal of heavy metal ions. However, it remains challenging to balance the efficient exposure of active sites and the stability of materials, and the potential mechanism of the interactions between heavy metal ions and the interface of MoSe 2 with different crystal phases and structures has yet to be comprehensively explored. Herein, mixed-phase 1T/2H MoSe 2 nanoflowers featured with ultrathin nanosheets, high ratio of 1T phase, enlarged interlayer spacing, and defect-rich structure have been synthesized and demonstrated excellent performance for removing Hg(II) and Pb(II) ions from aquatic system, including high capacity (952.4 mg·g−1 for Hg(II); 217.9 mg·g−1 for Pb(II)), rapid kinetics, superior selectivity, and anti-interference ability. The ultrathin nanosheets and enlarged interlayer spacing ensured efficient exposure of Se atoms; the high ratio of 1T phase was beneficial for the binding of heavy metal ions (as confirmed by DFT calculations). The defect-rich structure not only provided additional channels for ions diffusion, but also produced more active sites for ion binding and charge transfer. Benefiting from these structural characteristics, 1T/2H MoSe 2 could effectively and selectively remove Hg(II) and Pb(II) ions under the coexistence of various cations in practical water environment, the corresponding separation factors were greater than 170. Moreover, the interaction mechanism between two target ions and MoSe 2 was elucidated by experiment and DFT calculation. The present work not only explored advanced materials for the purification of heavy metal ions polluted water, but also may promote the exploration of MoSe 2 in environmental remediation. [ABSTRACT FROM AUTHOR]

The visualization analysis of dispersion state of the filler m silicone rubber was based on the fluorescent labeling and the laser scanning confocal microscope. The fluorescent silica microspheres were modified by different silane coupling agents, and the contact angle analysis, thermogravimetnc analysis and fluorescence spectroscopy were used to describe its surface properties. Both hydrophobic effect and bound rubber content of modified fluorescent silica microspheres are KH-570>KH-560>KH-550. Visual analysis results show that the aver- age size of aggregates and network connectivity of KH-570 modified fluorescent silica microspheres were 2.61 ̡m and 47%, KH-560 modified it were 2.95 /im and 43% and KH-550 modified it were 3.32 f(m and 41 %. The visual analysis method of the modified fluorescent SiO2 microsphere is beneficial to observe the dispersion state of it m the silicone rubber, and this method can statistically analyze the particle size of the modified fluorescent SiO2 microsphere aggregates. This method is helpful to evaluate the dispersion state of the filler m the silicone rubber. [ABSTRACT FROM AUTHOR]

Phosphoribosylformylglycinamidine synthase (PFAS) is an essential enzyme in de novo synthesis of purine. Previously, PFAS has been reported to modulate RIG-I activation during viral infection via deamidation. In this study, we sought to identify potential substrates that PFAS can deamidate. Flag-PFAS was transfected into HEK-293T cells and PFAS associated proteins were purified with anti-Flag M2 magnetic beads. PFAS associated proteins were identified using mass spectrometry and were analyzed using bioinformatics tools including KEGG pathway analysis, gene ontology annotation, and protein interaction network analysis. A total of 441 proteins is suggested to potentially interact with PFAS. Of this number, 12 were previously identified and 429 are newly identified. The interactions of PFAS with CAD, CCT2, PRDX1, and PHGDH were confirmed by co-immunoprecipitation and western blotting. This study is first to report the interaction of PFAS with several proteins which play physiological roles in tumor development including CAD, CCT2, PRDX1, and PHGDH. Furthermore, we show here that PFAS is able to deamidate PHGDH, and induce other posttranslational modification into CAD, CCT2 and PRDX1. The present data provide insight on the biological function of PFAS. Further study to explore the role of these protein interactions in tumorigenesis and other diseases is recommended. • Expression of PFAS can cause shifting of isoelectric point of some proteins. • A total of 429 proteins are newly identified to interact with PFAS. • PFAS interacts with CAD, CCT2, PRDX1, and PHGDH. • PFAS can induce deamidation of PHGDH and other PTM on CAD, CCT2, and PRDX1. [ABSTRACT FROM AUTHOR]

The quantitative structure–activity relationship models of 40 phenylhydrazine‐substituted tetronic acid derivatives were established between the 1H nuclear magnetic resonance (NMR) and 13C NMR chemical shifts and the antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis, and Colletotrichum capsici. The models were validated by R, R2, RA2, variance inflation factor, F, and P values testing and residual analysis. It was concluded from the models that the 13C NMR chemical shifts of C8, C10, C7, and the 1H NMR chemical shifts of Ha contributed positively to the activity against Fusarium graminearum, Botrytis cinerea, Colletotrichum capsici, and Rhizoctonia cerealis, respectively. The models indicated that decreasing the election cloud density of specific nucleuses in compounds, for example, by the substituting of electron withdrawing groups, would improve the antifungal activity. These models demonstrated the practical application meaning of chemical shifts in the quantitative structure–activity relationship study. Furthermore, a practical guide was provided for further structural optimization of the antifungal phenylhydrazine‐substituted tetronic acid derivatives based on the 1H NMR and 13C NMR chemical shifts. [ABSTRACT FROM AUTHOR]

Abstract Ovarian cancer is one of the most common gynecologic malignancies and has a poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of cancer development. Studies have shown that the dysregulation of lncRNAs is frequently observed in ovarian cancer and greatly contributes to malignant phenotypical changes. In this review, we provide perspectives on the involvement of lncRNAs in the proliferation, apoptosis, cell cycle, migration, invasion, metastasis and drug resistance of ovarian cancer based on recent discoveries. Then, we discuss the role of lncRNAs in predicting the prognosis of ovarian cancer. Finally, we provide insight into the potential of lncRNAs for evaluating the diagnosis and prognosis of ovarian cancer. Highlights • LncRNAs are non-protein-coding RNAs with length longer than 200 nt. • LncRNAs take a great part in proliferation, apoptosis, cell cycle, migration, invasion, metastasis and drug-resistance of ovarian cancer. • LncRNAs evaluate the diagnostic and prognostic value in ovarian cancer management. [ABSTRACT FROM AUTHOR]

In this study, a constitutive model based on microscopic physical mechanism of silicone rubber foams was established. A theoretical statistical model of rubber elasticity considering the effect of dangling chains was modified to build this model. When a strain amplification factor (X) was introduced, the theoretical model could fit the tensile stress-strain data of mono- and bi-modal foam matrix well (Adj. R-Square = 0.9989, 0.9983). Parameters related to the polymer network, namely, average molecular weight (Mc) and volume fraction (ϕ) of chain segments between adjacent cross-linking points (network strands), were calculated by probabilistic method from the number-average molecular weight (Mn), vinyl content (wVi) of the primary polysiloxanes and percent conversion (q) of vinyl groups. The primary and infinite strain amplification factors (X0, X∞) and decay exponent (z), introduced by X and related to the nanoparticles, were obtained by fitting. Inspired by the fact that the actual strain of matrix was lower than that of the foams’, we introduced another item, strain hysteresis item (H, related with the foam porosity and cell structure), into the statistical model as well. With the same above values of Mc, ϕ, X0 and X∞, the model could also fit the compressive stress-strain data of mono- and bi-modal foams well (Adj. R-Square = 0.9948, 0.9985). Interestingly, the strain hysteresis items of the mono- and bi-modal foams almost completely coincided under all experimental strains, which may be attributed to the almost equal porosity and similar cell structure of the two foams. This constitutive model may connect the macroscopic stress-strain behaviour to the parameters of microscopic molecular structures, promisingly providing a basis for the performance improvement and optimization of silicone rubber foams. [ABSTRACT FROM AUTHOR]

The filler network structure of the silica-reinforced silicone rubber was simulated by using the rare earth europium complex sensitized fluorescence enhancement technique. The filler network structure, curing performance and dynamic mechanical properties of the silica-reinforced silicone rubber were characterized by scanning electron microscopy, laser scanning confocal microscopy, rubber processing analyzer and solid rheological analyzer. The filler network connection rates of 30-60 parts of silica-filled silicone rubber were 31 %, 41 %, 58% and 70%, respectively, visualized by laser scanning confocal microscopy. The minimum torque (ML), characterization of filler-filler interaction, during the vulcanization process, the Payne effect and the shear storage modulus difference ΔG'(G'0--G'∞) in the strain sweep process were gradually increased. The results show that the filler network structure is gradually formed inside the silicone rubber with the increase of fillers, which is consistent with the obtained filler network connection rate, indicating that the combination of fluorescent labeling and laser scanning confocal microscopy can realize the visualization of the filler network structure in the silicone rubber. [ABSTRACT FROM AUTHOR]

The problem refers to an elastic infinite plate bounded by two oval holes, which is subjected to uniform surface tractions on the boundary of the holes and uniform tension and shear stress at infinity. By looking for a new mapping function, the considered region is conformally mapped onto an annulus, and a complex variable method is used to obtain the stress solution. The problem that an elastic infinite plate contains two circular holes or a circular hole and an oval hole is the special case of this article. The present solution has been validated by both published solutions for special cases and ANSYS software. Some computational examples are given to investigate the effects of the separation distance of the two holes, relative ratio of applied stresses, surface tractions on the boundaries, the size of a hole, shear stress at infinity and the loading orientation angle on the stress distribution of the hole boundaries. Practical significance of the solution is placed in the fact that it could be used as a quick-solver with high accuracy. [ABSTRACT FROM AUTHOR]

An analytical solution is presented for an elastic infinite plate containing an ellipse hole and a circle hole, which undergoes the internal traction along the holes and uniform tensions and shears at infinity. The solution uses the conformal transformation in complex functions, with the multiple connected region mapping onto a circular ring. The stress distribution solved for the infinite plane containing two unequal circle holes in prior literatures is the special case of this article. And contrast between the results of two unequal circle holes obtained by using the present analytical method and the Hoang's results is made in the article. As there is no analytical solution for two non-circular holes, the results obtained using the present analytical method are compared with the numerical results calculated by ANSYS. Computational examples given in this article has been analyzed to study the effect of distance between two holes, the ratio of stress in two directions at infinity, and the ratio of the major and minor axis, on the stress distribution of the hole boundary. [ABSTRACT FROM AUTHOR]

To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5.8% vs. 14.9%, P = 0.014; 94.2% vs. 85.1%, P = 0.014; 96.0% vs. 87.4%, P = 0.039). PRAME overexpression had no impact on outcome in T-ALL patients. Among B-ALL patients with non-poor cytogenetic risk, those with PRAME overexpression showed significantly lower CIR, higher DFS and OS rates at 3 years, respectively (8.47% vs. 14.5%, P = 0.009; 96.5% vs. 85.5%, P = 0.009; 98.4% vs. 88.0%, P = 0.023). Furthermore, PRAME overexpression was an independent good prognostic factor for relapse in all B-ALL patients and B-ALL patients with non-poor cytogenetic risk. Therefore, the prognostic significance of PRAME overexpression differed by ALL subtype; It predicted good outcome in pediatric B-ALL receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Pristine amino acid Zn-MOFs catalysts successfully catalyze Knoevenagel reactions in an eco‐friendly water/alcohol solution at room temperature and provide a recyclable and green approach to desired chemicals through basic catalysis. [Display omitted] • A series of pristine Zn-MOFs were synthesized through the reaction of Zn(II) salts with pyridyl amino acid derivatives. • The catalysts can promote Knoevenagel reactions in eco-friendly water/alcohol solvent media at room temperature. • These catalysts are recyclable and have good performance for an extended scope of benzaldehyde derivatives substrates. A series of zinc-based Metal-Organic Frameworks (MOFs) have been synthesized through the reaction of Zn(II) salts with amino acid derivatives Val-X [Val = N-(4-pyridylmethyl)- l -Valine, X = Cl−, HCOO−, CH 3 COO−] and Ala-X [Ala = N-(4-pyridylmethyl)- l -Alanine, X = Cl−, HCOO−]. The as-synthesized pristine Zn-MOFs adopt unique hexagonal coordination structures with robust amino and carboxylate sites. These pristine Zn-MOFs served as heterogeneous catalysts in Knoevenagel condensation reactions of aldehydes containing a variety of electron-donating and withdrawing groups with malononitrile or ethyl 2-cyanoacetate. These catalysts can promote these reactions in eco-friendly water/alcohol solvent media under mild conditions. High yields were achieved for both malononitrile and cyanoacetate products with E-isomer dominating for the latter. Furthermore, these catalysts can be recycled and reused for several times without losing catalytic activity significantly. [ABSTRACT FROM AUTHOR]

UDP-glucuronic acid dehydrogenase (UGD) and UDP-xylose synthase (UXS) are the two enzymes responsible for the biosynthesis of UDP-xylose from UDP-glucose. Several UGDs from bacterial sources, which oxidize UDP-glucose to glucuronic acid, have been found and functionally characterized whereas only few reports on bacterial UXS isoforms exist. Rhodothermus marinus, a halothermophilic bacterium commonly found in hot springs, proved to be a valuable source of carbohydrate active enzymes of biotechnological interest, such as xylanases, mannanases, and epimerases. However, no enzymes of R. marinus involved in the biosynthesis or modification of nucleotide sugars have been reported yet. Herein, we describe the cloning and characterization of two putative UGD (RmUGD1 and RmUGD2) and one UXS (RmUXS) isoform from this organism. All three enzymes could be expressed in recombinant form and purified to near homogeneity. UPLC- and NMR-based activity tests showed that RmUGD1 and RmUXS are indeed active enzymes, whereas no enzymatic activity could be detected by RmUGD2. Both RmUGD1 and RmUXS showed a temperature optimum of 60 °C, with almost no loss of activity after 1 h exposure at 70 °C. No metal ions were required for enzymatic activities. Zn ions strongly inhibited both enzymes. RmUGD1 showed higher salt tolerance and had a higher pH optimum than RmUXS. Furthermore, RmUGD1 was inhibited by UDP-xylose at higher concentrations. By coupling recombinant RmUXS and RmUGD1, UDP-xylose could be successfully synthesized directly from UDP-glucose. The high activity of the herein described enzymes make RmUGD1 and RmUXS the first thermo-tolerant biocatalysts for the synthesis of UDP-glucuronic acid and UDP-xylose. [ABSTRACT FROM AUTHOR]

Stress fields of a lined non-circular tunnel subjected to in situ stress are derived based on the complex variable method and on the assumption that the interface between the liner and surrounding rock is full-slip. The basic equations for solving the stress solutions are obtained according to the stress boundary condition along the inner boundary of the lining and the stress and normal displacement continuity conditions along the rock-lining interface. In the solving process, the support delay is also considered. The basic equations can be solved by the power series method, and the stresses in the surrounding rock mass and lining can be calculated. The distributions of the tangential stresses (also known as the circumferential stresses) along the excavation boundary and the inner boundary of the lining and the contact stresses along the rock-lining interface are analysed. An example demonstrates that the results are significantly affected by the number of terms in the power series. When the number of terms is greater than 100, the boundary conditions can be well satisfied, and the results of the stresses and displacements are highly accurate. The tangential stress results along the inner boundary of the lining for the full-slip condition are compared with those for the perfect bond condition, and the analysis indicates that the maximum value of the tangential stress for the full-slip condition is smaller than that for the perfect bond condition, which gives that the full-slip condition is superior to the perfect bond condition. Thus, the carrying capacity of the lining can be increased if sliding materials are installed between the lining and the surrounding rock mass. The analytic solutions are verified using computer simulation software. [ABSTRACT FROM AUTHOR]

This study investigated the impact of laparoscopic rectal cancer resection for patients with high operative risk, which was defined as American Society of Anesthesiology (ASA) grades III and IV. This study was conducted at a single center on patients undergoing rectal resection from 2006 to 2010. After screening by ASA grade III or IV, 248 patients who met the inclusion criteria were identified, involving 104 open and 144 laparoscopic rectal resections. The distribution of the Charlson Comorbidity Index was similar between the two groups. Compared with open rectal resection, laparoscopic resection had a significantly lower total complication rate ( P<.0001), lower pain rate ( P=.0002), and lower blood loss ( P<.0001). It is notable that the two groups of patients had no significant difference in cardiac and pulmonary complication rates. Thus, these data showed that the laparoscopic group for rectal cancer could provide short-term outcomes similar to those of their open resection counterparts with high operative risk. The 5-year actuarial survival rates were 0.8361 and 0.8119 in the laparoscopic and open groups for stage I/II (difference not significant), as was the 5-year overall survival rate in stage III/IV ( P=.0548). In patients with preoperative cardiovascular or pulmonary disease, the 5-year survival curves were significantly different ( P=.0165 and P=.0210), respectively. The cost per patient did not differ between the two procedures. The results of this analysis demonstrate the potential advantages of laparoscopic rectal cancer resection for high-risk patients, although a randomized controlled trial should be conducted to confirm the findings of the present study. [ABSTRACT FROM AUTHOR]

Temperature is one of the key parameters to determine the structures and properties of polymers during processing, but the effect of processing temperature on similar-structured polymer blends has rarely been reported. In this work, a linear low-density polyethylene (LLDPE)/ethylene-octene copolymer (EOC) blend with similar-structured components was chosen as a model system to study the effect of processing temperature (including compounding temperature and molding temperature) on its crystallization, phase morphology, and tensile behavior. It was found that the blends presented evenly distributed rubbery domains at lower processing temperatures, whereas a special, EOC-rich phase domain consisting of a less stable crystalline phase and a rubbery phase was observed at higher processing temperatures. The phase morphology was mainly determined by the final processing temperature, which had a major effect on the yield stress of the material. This work not only reports novel results on processing-structure-performance relations of similar-structured blends but can also guide the design and production of LLDPE-based products with tailored properties. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the applicability, safety, short-term and long-term outcomes of laparoscopic surgery in the treatment of right-sided colon carcinomas with D3 lymphadenectomy. Methods: Between June 2003 and September 2010, 324 patients with right-sided colon carcinoma underwent surgical treatment in the same hospital, 177 cases were treated by laparoscopic surgery (LRH group) and 147 cases by open surgery (ORH group). We performed a retrospective analysis of the differences between the two groups in terms of the clinical data. Results: There were no significant differences between the two groups in the demographic data; however, the recovery time was significantly shorter in the LRH group, the number of overall lymph nodes harvested and principle lymph nodes harvested in the LRH group was significantly higher than in the ORH group, the incidence of postoperative complications was 12.99 % in the LRH group and 22.45 % in the ORH group ( P < 0.05), and the recurrence rate in the LRH group was lower than that in the ORH group, although the difference was not significant (15.25 vs 19.73 %). The cumulative overall survival for all stages at 1, 3 and 5 years in the LRH group (97.18, 83.73 and 70.37 %) were not significantly different compared to those in the ORH group (94.56, 77.84 and 66.97 %). Conclusions: Laparoscopic-assisted right hemicolectomy with D3 lymphadenectomy for colon carcinomas is safe and effective, while it is also superior to open surgery regarding the short-term outcomes, and the long-term outcomes are similar to those of open surgery. [ABSTRACT FROM AUTHOR]

Blending polyethylene with thermoplastic polyolefin elastomers (TPOs) is a promising way to manipulate its structures and tailor its properties. Herein, three TPOs, i.e., two ethylene–octene copolymers (EOCs) and an olefin block copolymer (OBC) with different structures, were used to comparatively investigate the miscibility, crystallization, and phase behavior of their blends with a linear low-density polyethylene (LLDPE). It was found that large differences occurred in the crystallization and phase behaviors of the blends due to the different extent of similarity in the molecular structure between the TPO and the LLDPE matrix. In particular, a unique segregated phase morphology comprised a less stable crystalline phase and a rubbery phase was found in an LLDPE/EOC blend. The tensile performance and elasticity of the blends were also studied and correlated with the structures of the blends. This work not only provides novel results on the miscibility and phase behavior of the similar-structured LLDPE/TPO blends, but can also guide the design of LLDPE-based products with tailored performances. [ABSTRACT FROM AUTHOR]

Purposes: To study the feasibility, safety, and short-/long-term outcomes of laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy for colon cancer. Methods: The clinical data of 177 cases that underwent laparoscopy-assisted radical right hemicolectomy with D3 lymphadenectomy for colon cancer between Jun 2003 and Sep 2010 was collected; the safety of operation, status of recovery, complication, oncological outcomes, and results of short-/long-term follow-up were analyzed. Results: No case died in this study; five cases (2.82 %) were converted to open surgery. Four cases (2.26 %) underwent hand-assisted laparoscopic right hemicolectomy. The average operation time was 133 ± 36 min, and the blood loss was 94 ± 34 ml. The average time for passage of flatus, liquid food eating, and hospitalization were 2.1 ± 0.7, 3.2 ± 0.5, and 10.4 ± 2.7 day, respectively. The total number of lymph nodes removed was 15.2 ± 10.1. Postoperative complications were observed in 23 of 177 patients (12.99 %). The median follow-up period was 54 months; port-site recurrence was observed in one patient; local recurrence was found in five cases (2.82 %); distant metastasis was found in 21 cases (11.86 %). The cumulative overall survival of all stages at 12, 36, 60, and 72 months was 97.18 %, 83.73 %, 70.37 %, and 68.99 %, respectively. The cancer-specific survival was 98.73 % (12 months), 87.81 % (36 months), and 80.17 % (60 months). Conclusions: Laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy can be successfully performed for right colon cancer with the advantages of minimally invasive surgery. Moreover, the results implied appropriate short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Abstract: By using the semi-inverse method, an elastic plane stress solution of a lined vertical borehole in an isotropic ground due to non-axisymmetric in situ loads is presented. As two extreme cases, pure bond and pure slip boundary conditions, along the liner/ground interfaces have been implemented. The effect of elastic modulus of liner and ground and thickness of liner upon the stresses and displacements are analyzed. The result indicates that soft liner may alleviate the normal stress and shear stress acting on the liner outer surface. The maximum tangential compressive stresses and tensile stresses in liner for two extreme boundary cases occur on the inner and outer boundaries of liner. The shear stress reaches the maximum value at θ=45° and the harder the liner is, the greater the maximum value is. [Copyright &y& Elsevier]

A credit scoring method for a large problem not only achieves a certain accuracy but also its speed, interpretability, simplicity and other performance are also very important. In this paper, a novel method called an improved SVM learning algorithm based on three-variable working set (ISVMTV) is presented. This algorithm is derived by solving a series of the QP problems with only three points and the corresponding relaxation subproblems are solved analytically so that the proposed method approaches to the optimal solution more quickly. The proposed method is introduced to credit scoring and three datasets from UCI machine learning datasets are selected to demonstrate the method's competitive performance. Moreover, ISVM-TV shows a superior performance in saving the computational cost and improving classification accuracy. [ABSTRACT FROM AUTHOR]

Abstract: Analytical solutions are derived for the elastic–plastic stresses and strains around a circular tunnel subjected to an axial in situ stress, in a rock mass governed by the Mohr–Coulomb failure criterion. The calculation results show that the stresses, strains, and failure zones in the surrounding rock depend not only on the transverse in situ stress p but also on the axial in situ stress . The pattern of failure zones vary with different combinations of p and , which is different from the results produced by earlier plane strain analyses. If is less than some critical value, the radius of the plastic zones are the same as give by the plane strain analysis, and depends only on p. If exceeds the critical value, the radius of the plastic zone increases with increasing . The analytical solutions are verified by three-dimensional numerical analyses using FLAC3D software. [Copyright &y& Elsevier]

Abstract: The equilibrium melting temperature (Tm ), through linear extrapolation method (HW) and nonlinear extrapolation method (MX) respectively, and the supercooling dependence of the spherulitic growth rate, in the context of the Lauritzen–Hoffman secondary nucleation theory, of poly(phenylene sulfide) (PPS) have been investigated by differential scanning calorimeter (DSC) and a polarized optical microscope (POM) equipped with a CSS450 shear hot stage. The results show that the Tm value obtained by MX method is more suitable for analyzing the regime transition behavior of PPS than that by HW method. And the regime I/II and II/III transitions can be really observed at TX =526 and TX =516K, respectively, while analyzing the secondary nucleation theory of PPS by use of the Tm value obtained by MX method. [Copyright &y& Elsevier]

Abstract: A novel adsorbent was prepared by immobilizing Fe(III) onto collagen fiber matrix, and its adsorption to lysozyme was studied. Fe(III) was uniformly dispersed in collagen fibers mainly through chemical reaction and could endure the extraction of water. It was found that the Fe(III)-immobilized collagen fiber (FICF) exhibited high adsorption capacity to lysozyme. The adsorption capacity was 395mg/g at 303K when initial concentration of lysozyme was 2.5mg/mL. The adsorption capacity was significantly influenced by pH, and it reached a maximum value around pH 8.0. The adsorption capacity increased with the increase of temperature. The adsorption capacity of lysozyme remarkably decreased when the concentration of NaCl was increased from 0 to 0.25mol/L. However, the adsorption capacity increased slightly as the concentration of NaCl was further increased. The adsorption isotherms can be described by the Langmuir equation. Further analysis indicated that the adsorption kinetic data can be well fitted by the pseudo-second-order rate model, and the adsorption capacities calculated by the model were consistent with those of the actual measurements. In addition, Fe(III)-immobilized collagen fiber presented excellent column adsorption kinetic properties and high binding capacity. The adsorption behavior of the column was almost unchanged in adsorption–desorption cycles. The purification of lysozyme from chicken egg white powder by using FICF was investigated. The purity of lysozyme obtained was 100%, and recovery extent of lysozyme was 70.5%. [Copyright &y& Elsevier]

Aiming to reveal structural mechanisms and filler fraction on energy dissipation of Mullins effect in silicone rubber, in situ tension small angle X-ray scattering (SAXS) were conducted. Two fractions of silica, 18.4 % (S50) and 26.5 % (S80), were utilized for variable amplitude loading investigation. The aggregates of both S50 and S80 keep as a stiff and stable unit with sizes of 53 nm and 45 nm during cyclic deformation, respectively. While the correlation lengths (CL) of both samples arise when the nominal strain (ɛ) surpasses 1.5, and increase from 108 nm to 126 nm and 100 nm–122 nm, respectively. The maximum stress and the normalized recovery hysteresis energy (E r h / E t o t a l ) behaviors likewise exhibit a strain threshold. E r h / E t o t a l (S 50) > E r h / E t o t a l (S 80) in all cycles prior to the ɛ of 1.0. When the ɛ surpasses 1.5, E r h / E t o t a l (S 50) < E r h / E t o t a l (S 80) for the first loop of each strain region. Hence, combining with the constitutive model analysis, the strain threshold for rubber matrix and filler network to each dominate the response to outfield loading were explored, along with the crucial impacts of filler percentage on different loading histories and extents. [Display omitted] • Mechanisms of Mullins effect was studied via SAXS and constitutive model. • The filler network dominated energy dissipation in larger strain. • Higher filler fraction sample is more susceptible to impact in small strain. [ABSTRACT FROM AUTHOR]

• We use emotion and intention to decide the tactics of visual interaction dynamically. • The battleship operator gets key information from complex situation map efficiently. • A method for fusion analysis of target intention and operator emotion is presented. • The model can provide intelligent scheme for target visualization according to situation change. • The model improves operator's ability to perceive and understand the battlefield. Due to the complexity of situation information and the diversity of display modes, the traditional battleship information system cannot provide the operator with important information effectively, which leads to its low ability to express the details of target intentions. Therefore, taking air targets as the main research object, this paper proposes a battleship human-machine intelligent interaction model based on the fusion of target intention and operator emotion. The model mainly includes four modules: the intention recognition of the target, the emotion cognition of the operator, the fusion of the intention and the emotion, and the interactive visualization. The goal is to provide a personalized human-machine interaction scheme that can realize auxiliary decision-making and man-machine integration intelligence according to the target intention and the operator's emotion. Finally, the evaluation results have demonstrated the feasibility and reliability of the proposed model. [Display omitted] [ABSTRACT FROM AUTHOR]

This paper presents a method to solve the stress field of a deep buried circular lining tunnel under the combined action of an unsteady temperature field and in situ stress. The solution of the temperature field can be reduced to a problem of solving the unsteady temperature field in the composite medium under the first type of boundary conditions in the infinite domain, and the distribution of the temperature field in the lining and surrounding rock can be obtained by the Laplace transform method. Through the stress boundary condition of the inner boundary of the lining, the continuous condition of the contact surface and the zero displacement boundary condition at infinity, equations expressed by the boundary values of the analytical functions are established. Then the temperature stresses caused by temperature changes can be obtained. By superimposing these stresses with the stresses caused by in situ stress, the total stresses inside the lining and surrounding rock can be obtained. This article compares the analytical solutions with the numerical solutions obtained by ANSYS. In addition, the influence of temperature field on the stress field of lining and surrounding rock is discussed in the case of temperature decrease and increase through calculation examples. [ABSTRACT FROM AUTHOR]

Abstract: Silicone rubbers were successfully foamed by supercritical carbon dioxide (SC CO2). Samples were precured and fully cured before and after the basic foaming process with SC CO2. The effects of precuring time and soaking pressure on the density and pore morphology of prepared silicone rubber foams were investigated. It was found that a crosslinked network structure affected by precuring time played an important role in the foaming process. In current study, 5min was the optimum precuring time for foaming and the corresponding minimum sample density was 0.239g/cm3. The best prepared foam had polygonal pores and the pores were interconnected. Our results indicate that SC CO2 foaming technology can be used to prepare crosslinked elastomer foams by appropriately controlling the crosslinked network structure. [Copyright &y& Elsevier]

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068–136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy. Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818. [ABSTRACT FROM AUTHOR]

• Compared the HtSDS and △HtSDS at the start of treatment and during follow-up period. • Compared the adult height and median parental height(MPH). • Further compared the HtSDS classified by age and gender in imatinib group. • The influencing factors on the deceleration of height growth by imatinib. To investigate the effect of tyrosine kinase inhibitors (TKIs) on the statural growth in children with acute lymphoblastic leukemia (ALL). We retrospectively collected data from 344 children with ALL younger than 17 years old at diagnosis identified in pediatric department of Peking University People's Hospital. The children were divided into three groups: conventional chemotherapy group, imatinib group and dasatinib group. Height was expressed as standard deviation score(HtSDS). In the three groups, we compared the HtSDS and △HtSDS at the start of treatment and during follow-up period and also compared the adult height and median parental height(MPH). We further compared the HtSDS classified by age and gender in imatinib group. At last, univariate analysis was used to analyze the influencing factors on the deceleration of height growth by imatinib. There were 298 children in conventional chemotherapy group, 39 in imatinib group and 7 in dasatinib group. In imatinib group, the mean HtSDS of children at follow-up time was significantly lower than that at the start of treatment (P < 0.05), regardless of age and gender. In imatinib group, the decrease of HtSDS in girls was more obvious than in boys(P = 0.031). The HtSDS gradually decreased in the first and the second year in imatinib group. After discontinuation of imatinib, the HtSDS had no obvious change. Multivariate analysis showed that the HtSDS at the start of imatinib was negatively correlated with severe growth impairment on imatinib therapy. The HtSDS in dasatinib group and conventional chemotherapy group maintained a high degree of consistency. Imatinib can affect growth velocity in children with ALL, regardless of age and gender. With the discontinuation of imatinib, the inhibitory effect will not continue. The lower HtSDS at the start of imatinib therapy, the more obvious effect of imatinib on growth impairment will be, and the effect will be more obvious in girls than boys. [ABSTRACT FROM AUTHOR]

Drug discovery and development constitute a laborious and costly undertaking. The success of a drug hinges not only good efficacy but also acceptable absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties. Overall, up to 50% of drug development failures have been contributed from undesirable ADMET profiles. As a multiple parameter objective, the optimization of the ADMET properties is extremely challenging owing to the vast chemical space and limited human expert knowledge. In this study, a freely available platform called Chemical Molecular Optimization, Representation and Translation (ChemMORT) is developed for the optimization of multiple ADMET endpoints without the loss of potency (https://cadd.nscc-tj.cn/deploy/chemmort/). ChemMORT contains three modules: Simplified Molecular Input Line Entry System (SMILES) Encoder, Descriptor Decoder and Molecular Optimizer. The SMILES Encoder can generate the molecular representation with a 512-dimensional vector, and the Descriptor Decoder is able to translate the above representation to the corresponding molecular structure with high accuracy. Based on reversible molecular representation and particle swarm optimization strategy, the Molecular Optimizer can be used to effectively optimize undesirable ADMET properties without the loss of bioactivity, which essentially accomplishes the design of inverse QSAR. The constrained multi-objective optimization of the poly (ADP-ribose) polymerase-1 inhibitor is provided as the case to explore the utility of ChemMORT. [ABSTRACT FROM AUTHOR]

In the process of drug discovery, the optimization of lead compounds has always been a challenge faced by pharmaceutical chemists. Matched molecular pair analysis (MMPA), a promising tool to efficiently extract and summarize the relationship between structural transformation and property change, is suitable for local structural optimization tasks. Especially, the integration of MMPA with QSAR modeling can further strengthen the utility of MMPA in molecular optimization navigation. In this study, a new semi-automated procedure based on KNIME was developed to support MMPA on both large- and small-scale datasets, including molecular preparation, QSAR model construction, applicability domain evaluation, and MMP calculation and application. Two examples covering regression and classification tasks were provided to gain a better understanding of the importance of MMPA, which has also shown the reliability and utility of this MMPA-by-QSAR pipeline. [ABSTRACT FROM AUTHOR]

In the process of drug discovery, the optimization of lead compounds has always been a challenge faced by pharmaceutical chemists. Matched molecular pair analysis (MMPA), a promising tool to efficiently extract and summarize the relationship between structural transformation and property change, is suitable for local structural optimization tasks. Especially, the integration of MMPA with QSAR modeling can further strengthen the utility of MMPA in molecular optimization navigation. In this study, a new semi-automated procedure based on KNIME was developed to support MMPA on both large- and small-scale datasets, including molecular preparation, QSAR model construction, applicability domain evaluation, and MMP calculation and application. Two examples covering regression and classification tasks were provided to gain a better understanding of the importance of MMPA, which has also shown the reliability and utility of this MMPA-by-QSAR pipeline. [ABSTRACT FROM AUTHOR]

• Analytical solution for shallow tunnel with point anchored rockbolts is presented. • The mechanical contribution of rockbolts is analyzed quantitatively. • The effect of parameters on axial load is discussed. • The interaction between surrounding rock and rockbolts is considered. In this paper, an analytical approach is presented, by focusing on the shallow buried tunnel reinforced by two-point anchored rockbolts, by considering the rockbolts as two identical concentrated forces acting in opposite directions, applied at both the ends of the rockbolts. It was assumed that the surrounding rock and the bolts were in an elastic state and the problem existed in a plane strain condition. The complex variable method was applied to reach a solution. While solving the problem, first, the problem of a circular shallow buried tunnel, with a concentrated force acting on the surrounding rock mass, was addressed. Afterwards, the solution for a tunnel reinforced by multiple rockbolts was obtained, based on the previous solution, considering that displacements between the rockbolts and rock mass were compatible. The case of pre-stressed rockbolts was also considered in this paper. The solution obtained in this paper provides the results for the axial load of the rockbolts and the stress and displacement of the surrounding rock. The analytical solution results were found to be similar to that of the finite element method obtained by ANSYS software. In addition, to quantify the mechanical contribution of the rockbolts, the stress and displacement distributions of the surrounding rock, for reinforced tunnel and non-reinforced tunnel, were also compared. [ABSTRACT FROM AUTHOR]

The relaxation behaviors and impact damping effects of phenyl silicone rubber were investigated using dynamic mechanical analysis (DMA) and a home-designed impact damping test. The effects of rubber phenyl content, sample thickness and compression on the damping performance were evaluated. DMA results over a broad temperature and frequency range indicate that silicone rubber with higher phenyl content would overall exhibit better damping capacity owing to the increase in friction between molecular chains, and the impact damping performances agree well with the relaxation results. Besides, sample thickness and compression will also strongly influence the damping performances as directly evidenced by the impact damping tests. It is demonstrated that a combination of DMA and impact damping test is of critical use for designing rubber damping devices according to the frequency range of interest. This work will provide deeper insight into damping performances of rubbers and practical guidance for their engineering applications. • The "true" impact damping effects of silicone rubbers under work conditions were evaluated using impact damping test. • The impact damping results were correlated with DMA relaxation results. • The loss peak area of silicone rubber will increase almost linearly with phenyl content. • Sample thickness will strongly influence the damping effect at a certain frequency. • Compression will lower the damping effect at high frequencies, but enhance the damping effect at lower frequencies. [ABSTRACT FROM AUTHOR]

This paper presents an effective optimization approach based on the equi-stress criterion and conformal transformation to determine two equi-stress holes with different areas in an infinite plate subjected to biaxial loads at infinity and internal uniform pressure on hole boundaries. Conformal transformation in the complex variable method is used to map the outer domain of two holes in the physical plane onto an annulus in the image plane. Mathematically, the hole shapes are parameterized and expressed in one mapping function, therefore, the shape of two holes can be determined by obtaining the coefficients of the mapping function. In the process of optimization, the coefficients are used as design variables in the differential evolution (DE) algorithm to determine the hole shapes. As examples, the results has high accuracy, the optimal hole shapes under different conditions are given and the effect of each parameter are analyzed. What's more, the contour plots of principal stresses are presented to clearly show the stress distribution in the domain for the optimal hole shape. • Obtaining the shape of two equi-stress holes with different areas. • The equi-stress criterion and conformal transformation were used. • The process is simple and the scope of application is wide. • Presenting the hole shapes for different parameters. • Presenting the stress filed of the domain. [ABSTRACT FROM AUTHOR]

Introduction: Residual disease (RD) detected using multiparametric flow cytometry (MFC) is an independent predictive variable of relapse in acute myeloid leukaemia (AML). However, RD thresholds and optimal assessment time points remain to be validated. Material and methods: We investigated the significance of RD after induction therapy in paediatric AML with normal karyotype between June 2008 and June 2018. Bone marrow samples from 73 patients were collected at the end of the first (BMA‐1) and second (BMA‐2) induction courses to monitor RD using MFC. Results: Presence of RD after BMA‐1 and/or BMA‐2 correlated with poor relapse‐free (RFS) and overall survival at 0.1% RD cutoff level. Receiver operating characteristic curve showed that RD cutoff levels of 1.3% and 0.5% after BMA‐1 and BMA‐2, respectively, predicted events with the highest sensitivity and specificity. In multivariable analysis, RD after BMA‐2 was the strongest independent risk predictor for poor RFS (hazard ratio 2.934; 95% confidence interval: 1.106‐7.782; P =.031). Conclusions: Our study therefore suggests that an RD level ≥0.5% after BMA‐2 has a significant predictive impact on the prognosis of AML patients having normal karyotype and thus guide the stratification of treatment strategies. [ABSTRACT FROM AUTHOR]

Background High-throughput screening (HTS) and virtual screening (VS) have been widely used to identify potential hits from large chemical libraries. However, the frequent occurrence of 'noisy compounds' in the screened libraries, such as compounds with poor drug-likeness, poor selectivity or potential toxicity, has greatly weakened the enrichment capability of HTS and VS campaigns. Therefore, the development of comprehensive and credible tools to detect noisy compounds from chemical libraries is urgently needed in early stages of drug discovery. Results In this study, we developed a freely available integrated python library for negative design, called Scopy, which supports the functions of data preparation, calculation of descriptors, scaffolds and screening filters, and data visualization. The current version of Scopy can calculate 39 basic molecular properties, 3 comprehensive molecular evaluation scores, 2 types of molecular scaffolds, 6 types of substructure descriptors and 2 types of fingerprints. A number of important screening rules are also provided by Scopy, including 15 drug-likeness rules (13 drug-likeness rules and 2 building block rules), 8 frequent hitter rules (four assay interference substructure filters and four promiscuous compound substructure filters), and 11 toxicophore filters (five human-related toxicity substructure filters, three environment-related toxicity substructure filters and three comprehensive toxicity substructure filters). Moreover, this library supports four different visualization functions to help users to gain a better understanding of the screened data, including basic feature radar chart, feature-feature-related scatter diagram, functional group marker gram and cloud gram. Conclusion Scopy provides a comprehensive Python package to filter out compounds with undesirable properties or substructures, which will benefit the design of high-quality chemical libraries for drug design and discovery. It is freely available at https://github.com/kotori-y/Scopy. [ABSTRACT FROM AUTHOR]

KRAS is one of the leading mutations reported in colon cancer. However, there are few studies on the application of KRAS related signature in predicting prognosis and drug sensitivity of colon cancer patient. We identified KRAS related differentially expressed genes (DEGs) using The Cancer Genome Atlas (TCGA) database. A signature closely related to overall survival was recognized with Kaplan–Meier survival analysis and univariate cox regression analysis. Then we validated this signature with overall expression score (OE score) algorithm using both scRNA-seq and bulk RNA-seq data. Based on this signature, we performed LASSO cox regression to establish a prognostic model, and corresponding scores were calculated. Differences in genomic alteration, immune microenvironment, drug sensitivity between high- and low-KRD score groups were investigated. A KRAS related signature composed of 80 DEGs in colon cancer were recognized, among which 19 genes were selected to construct a prognostic model. This KRAS related signature was significantly correlated with worse prognosis. Furthermore, patients who scored lower in the prognostic model presented a higher likelihood of responding to chemotherapy, targeted therapy and immunotherapy. Furthermore, among the 19 selected genes in the model, SPINK4 was identified as an independent prognostic biomarker. Further validation in vitro indicated the knockdown of SPINK4 promoted the proliferation and migration of SW48 cells. In conclusion, a novel KRAS related signature was identified and validated based on clinical and genomic information from TCGA and GEO databases. The signature was proved to regulate genomic alteration, immune microenvironment and drug sensitivity in colon cancer, and thus might serve as a predictor for individual prognosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT.Methods: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed.Results: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009).Conclusions: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis. [ABSTRACT FROM AUTHOR]

• The recognition of frequent hitters remains a challenge in early drug discovery. • The commonly underlying mechanisms of frequent hitters are reviewed. • Experimental detection techniques and computational prediction models for frequent hitters are introduced. • Rational and efficient application of frequent hitters computational models is worthy discussing. One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved. The recognition of frequent hitters is one of the major challenges in early drug discovery. Here, we discuss underlying mechanisms, experimental detection techniques, computational prediction models and their rational use. [ABSTRACT FROM AUTHOR]