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Modern electronic structure theory is built around the Born–Oppenheimer approximation and the construction of an electronic Hamiltonian H ̂ e l (X) that depends on the nuclear position X (and not the nuclear momentum P). In this article, using the well-known theory of electron translation (Γ′) and rotational (Γ″) factors to couple electronic transitions to nuclear motion, we construct a practical phase-space electronic Hamiltonian that depends on both nuclear position and momentum, H ̂ P S (X , P). While classical Born–Oppenheimer dynamics that run along the eigensurfaces of the operator H ̂ e l (X) can recover many nuclear properties correctly, we present some evidence that motion along the eigensurfaces of H ̂ P S (X , P) can better capture both nuclear and electronic properties (including the elusive electronic momentum studied by Nafie). Moreover, only the latter (as opposed to the former) conserves the total linear and angular momentum in general. [ABSTRACT FROM AUTHOR]

We show that standard Ehrenfest dynamics does not conserve linear and angular momentum when using a basis of truncated adiabatic states. However, we also show that previously proposed effective Ehrenfest equations of motion [M. Amano and K. Takatsuka, "Quantum fluctuation of electronic wave-packet dynamics coupled with classical nuclear motions," J. Chem. Phys. 122, 084113 (2005) and V. Krishna, "Path integral formulation for quantum nonadiabatic dynamics and the mixed quantum classical limit," J. Chem. Phys. 126, 134107 (2007)] involving the non-Abelian Berry force do maintain momentum conservation. As a numerical example, we investigate the Kramers doublet of the methoxy radical using generalized Hartree–Fock with spin–orbit coupling and confirm that angular momentum is conserved with the proper equations of motion. Our work makes clear some of the limitations of the Born–Oppenheimer approximation when using ab initio electronic structure theory to treat systems with unpaired electronic spin degrees of freedom, and we demonstrate that Ehrenfest dynamics can offer much improved, qualitatively correct results. [ABSTRACT FROM AUTHOR]

Alumni can offer authentic perceptions of how university education is relevant to career requirements with direct educational experiences and frontline work experiences. This study captures the experiences of alumni in the engineering field to illuminate the multi-faceted distinctions between the higher education and employment systems. Based on semi-structured interviews and artefact collection, the findings reveal that the university system focuses more on fragmented and theoretical knowledge in course goals, using classical textbooks as the main means of instruction, while the workplace system emphasises the whole picture and application competence, using cutting-edge instruments and project-based approaches to enhance employees' abilities. Students at universities are less incentivised to work hard and collaborate with each other than employees at companies due to different incentive rules and different community milieu. The workplace system also has a better division of labour than universities in cultivating talents. Practical implications are discussed regarding aspects of higher education reform. [ABSTRACT FROM AUTHOR]

Background: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. Methods: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4−CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. Results: The percentages of patients in none CTC, OCT4−CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4−CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4−CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4−CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. Conclusion: OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment. [ABSTRACT FROM AUTHOR]

A systematic experimental study has been conducted on the simulated intercritical coarse‐grained heat affected zone of 690 MPa grade heavy‐plate medium Mn steel by tailoring heat input of the first welding pass to obtain the influence of initial microstructure on the austenite reversion mechanism, recrystallization, and resultant impact toughness. Results reveal that prior austenite grain size significantly increases from 30 ± 11, 41 ± 14 to 54 ± 15 μm with the increasing heat input from 15, 30 to 50 kJ cm−1, which affect the nucleation site of reversed austenite, recrystallization mechanism, and final microstructure. Accordingly, impact toughness is better at the heat input of 30 kJ cm−1 (75.2 ± 0.8 J) in comparison with that of 15 kJ cm−1 (63.3 ± 13.3 J) and 50 kJ cm−1 (26.7 ± 6.5 J) at −40 °C, which is mainly ascribed to the formation of lamellar heterogeneous structures, multiplication of slip system and morphology of high‐angle grain boundaries. [ABSTRACT FROM AUTHOR]

We propose an efficient version of ensemble Hartree–Fock/density functional theory to calculate a set of two charge-transfer states for systems with odd-numbers of electrons. The approach does require definitions of donor/acceptor fragments; however, the approach is not very sensitive to such definitions—even in the limit of very strong electronic coupling. The key ansatz is that, by mandating that the vector space spanned by the active orbitals projects equally onto the donor and acceptor fragments, such a constraint eliminates all intra-molecular local excitations and makes it far easier to generate potential energy surfaces that are smooth over a wide region of configuration space. The method is fast, working with only two electron configurations, and should be useful for ab initio non-adiabatic dynamics in the near future. [ABSTRACT FROM AUTHOR]

The nuclear–electronic orbital (NEO) method is a multicomponent quantum chemistry theory that describes electronic and nuclear quantum effects simultaneously while avoiding the Born–Oppenheimer approximation for certain nuclei. Typically specified hydrogen nuclei are treated quantum mechanically at the same level as the electrons, and the NEO potential energy surface depends on the classical nuclear coordinates. This approach includes nuclear quantum effects such as zero-point energy and nuclear delocalization directly into the potential energy surface. An extended NEO potential energy surface depending on the expectation values of the quantum nuclei incorporates coupling between the quantum and classical nuclei. Herein, theoretical methodology is developed to optimize and characterize stationary points on the standard or extended NEO potential energy surface, to generate the NEO minimum energy path from a transition state down to the corresponding reactant and product, and to compute thermochemical properties. For this purpose, the analytic coordinate Hessian is developed and implemented at the NEO Hartree–Fock level of theory. These NEO Hessians are used to study the SN2 reaction of ClCH3Cl− and the hydride transfer of C4H9+. For each system, analysis of the single imaginary mode at the transition state and the intrinsic reaction coordinate along the minimum energy path identifies the dominant nuclear motions driving the chemical reaction. Visualization of the electronic and protonic orbitals along the minimum energy path illustrates the coupled electronic and protonic motions beyond the Born–Oppenheimer approximation. This work provides the foundation for applying the NEO approach at various correlated levels of theory to a wide range of chemical reactions. [ABSTRACT FROM AUTHOR]

Within the context of fewest-switch surface hopping (FSSH) dynamics, one often wishes to remove the angular component of the derivative coupling between states J and K . In a previous set of papers, Shu et al. [J. Phys. Chem. Lett. 11, 1135–1140 (2020)] posited one approach for such a removal based on direct projection, while we isolated a second approach by constructing and differentiating a rotationally invariant basis. Unfortunately, neither approach was able to demonstrate a one-electron operator O ̂ whose matrix element J O ̂ K was the angular component of the derivative coupling. Here, we show that a one-electron operator can, in fact, be constructed efficiently in a semi-local fashion. The present results yield physical insight into designing new surface hopping algorithms and are of immediate use for FSSH calculations. [ABSTRACT FROM AUTHOR]

Multicomponent density functional theory (DFT) has many practical advantages for incorporating nuclear quantum effects into quantum chemistry calculations. Within the nuclear-electronic orbital (NEO) framework, specified nuclei, typically protons, are treated quantum mechanically on the same level as the electrons. Previously, electron-proton correlation functionals based on the local density approximation (LDA), denoted epc17 and epc18, were developed and shown to provide more accurate proton densities and energies compared to the neglect of electron-proton correlation, but a quantitatively accurate description of both densities and energies simultaneously has remained elusive. Herein, an electron-proton correlation functional that depends on the electron and proton density gradients, as well as the densities, is derived and implemented. Compared to the LDA functionals, the resulting generalized gradient approximation functional, denoted epc19, is able to simultaneously provide accurate proton densities and energies, as well as reproduce the impact of nuclear quantum effects on optimized geometries. In addition, without further parameterization, the NEO-DFT/epc19 method provides accurate densities and energies for deuterium as well as hydrogen. These results demonstrate that the form of the epc19 functional is able to capture the essential aspects of electron-proton correlation and highlights the importance of including gradient terms. This approach will enable the exploration of nuclear quantum effects and isotope effects in a wide range of systems. [ABSTRACT FROM AUTHOR]

The continuous cooling tnsformation of deformed austenite and relationship to mechanical properties in medium-Mn steel was investigated by combining thermomechanical controlled processing and continuous cooling processes. The results indicated that the microstructure of experimental steel consists of lath martensite and a small amount of retained austenite. The stability of austenite was significantly improved by manganese, and martensite tnsformation occurred only during the slowly furnace-cooling process. The morphology of prior austenite gins changed from equiaxed recrystallization type to flat-elongated type with decreasing rolling tempeture. The martensitic tnsformation tempeture was decreased by the fgmentation of prior austenite gins and the stin hardening introduced by hot rolling, resulting in refined martensitic laths. The excellent mechanical properties were obtained in the steel rolled in the non-recrystallization region with combination of yield strength of 910 MPa, ultimate tensile strength of 1288 MPa and Vickers hardness number of 386.4 HV, which were mainly attributed to the refined martensitic laths, high density dislocation in matrix and high gin boundary length per unit area. [ABSTRACT FROM AUTHOR]

Purpose. Outbreaks caused by infectious diseases are now serious public health events. At present, most hospitals have a high number of fever clinic attendances. In order to improve the efficiency of fever clinic screening, timely detection and control of infection sources, early detection, early isolation, and early treatment, our hospital explored the construction and effect of our fever clinic management model during the response period by constructing a fever clinic regular management model based on the principles of infection control. Methods. 1300 cases (September 2021 to February 2022) with or without epidemiological history were divided into the control group (without epidemiological history) and the observation group (with epidemiological history) and patients were given differentiated management. A model of permanent management of a fever clinic during the epidemic was set up and evaluated by implementing the person responsible for epidemic positions, optimizing tertiary care, and strengthening nosocomial infection protection for health care workers. Results. The results showed that patients in the observation group had a lower age of onset, a longer consultation time, and a higher proportion of patients with fever, which was different from the control group (P < 0.05). Compared with the control group, the proportion of routine blood tests, the proportion of four respiratory virus tests, and the per capita cost were higher in the observation group, and the differences were statistically significant (P < 0.05). There were no missed diagnoses, underreporting, cross-infections, or nosocomial infections in either group, and there were no significant differences between the two groups in terms of patients' evaluation of management quality and satisfaction with management (P > 0.05). The skill level, management attitude, and standardized operation of outpatient clinic managers improved after the construction of a fever clinic standing management model based on infection control, and the recognition of patients was higher in the observation group (P < 0.05). Conclusion. The construction of a fever outpatient routine management model based on the principle of infection control is conducive to the standardized implementation of the management and treatment of health care workers, early detection of the source of transmission to cut off the transmission route, avoiding cross-infection and nosocomial infection, and ensuring the safety of patients and health care workers. [ABSTRACT FROM AUTHOR]

The thyroid nodule segmentation of ultrasound images is a critical step for the early diagnosis of thyroid cancers in clinics. Due to the weak edge of ultrasound images and the complexity of thyroid tissue structure, it is still challenging to accurately segment the delicate contour of thyroid nodules. A local and context-attention adaptive network (LCA-Net) for thyroid nodule segmentation is proposed to address these shortcomings, which leverages both local feature information from convolution neural networks and global context information from transformers. Firstly, since most existing thyroid nodule segmentation models are skilled at local detail features and lose some context information, we propose a transformers-based context-attention module to capture more global associative information for the network and perceive the edge information of the nodule contour. Secondly, a backbone module with 7 × 1 , 1 × 7 convolutions and the activation function Mish is designed, which enlarges the receptive field and extracts more feature details. Furthermore, a nodule adaptive convolution (NAC) module is introduced to adaptively deal with thyroid nodules of different sizes and positions, thereby improving the generalization performance of the model. Simultaneously, an optimized loss function is proposed to solve the pixels class imbalance problem in segmentation. The proposed LCA-Net, validated on the public TN-SCUI2020 and TN3K datasets, achieves Dice scores of 90.26% and 82.08% and PA scores of 98.87% and 96.97%, respectively, which outperforms other state-of-the-art thyroid nodule segmentation models. This paper demonstrates the superiority of the proposed LCA-Net for thyroid nodule segmentation, which possesses strong generalization performance and promising segmentation accuracy. Consequently, the proposed model has wide application prospects for thyroid nodule diagnosis in clinics. [ABSTRACT FROM AUTHOR]

We investigate the Galerkin spectral approximation of an optimal control problem governed by a fourth-order partial differential equation (PDE), in which an L 2 -norm constraint on control variable is equipped. First, the optimality conditions for both the original control problem and its spectral approximation problem are, respectively, obtained. Then, a priori error estimates of the spectral approximation problem are established in detail. Next, a posteriori error estimates for the approximation problem are also investigated, which include not only H 2 -error estimate for the state and co-state but also L 2 -error estimate for the control, state and co-state. Finally, three numerical examples are executed to validate the theoretical analysis. [ABSTRACT FROM AUTHOR]

Large yellow croaker iridovirus (LYCIV) poses a growing threat to large yellow croaker (Larimichthys crocea) aquaculture, requiring early diagnosis for effective prevention and control. However, current detection methods are time-consuming, labor-intensive, or require specialized equipment, hindering timely diagnosis. To address this concern, we developed a novel platform combining CRISPR/Cas12a and recombinase polymerase amplification (RPA) for rapid and sensitive LYCIV detection. Our strategy targeted the conserved ATPase gene, utilizing specific crRNA and RPA primers for selective detection. Additionally, we employed a lateral flow strip technique for intuitive visual assessment. The performance evaluation demonstrated outstanding specificity and sensitivity, with a limit of detection as low as 5 × 103 copies / reaction of iridovirus. Validation on spiked and clinical fish samples confirmed the accuracy through PCR analysis. Overall, our developed platform offers a convenient, on-site, and user-friendly tool for early diagnosis, prevention, and control of LYCIV-related diseases in large yellow croaker aquaculture. • A CRISPR/Cas12a-powered platform was developed to detect large yellow croaker iridovirus. • The specific crRNAs and RPA primers were designed to target the ATPase gene. • This platform was a convenient, on-site, and user-friendly iridovirus detection tool. [ABSTRACT FROM AUTHOR]

For a system without spin–orbit coupling, the (i) nuclear plus electronic linear momentum and (ii) nuclear plus orbital electronic angular momentum are good quantum numbers. Thus, when a molecular system undergoes a nonadiabatic transition, there should be no change in the total linear or angular momentum. Now, the standard surface hopping algorithm ignores the electronic momentum and indirectly equates the momentum of the nuclear degrees of freedom to the total momentum. However, even with this simplification, the algorithm still does not conserve either the nuclear linear or the nuclear angular momenta. Here, we show that one way to address these failures is to dress the derivative couplings (i.e., the hopping directions) in two ways: (i) we disallow changes in the nuclear linear momentum by working in a translating basis (which is well known and leads to electron translation factors) and (ii) we disallow changes in the nuclear angular momentum by working in a basis that rotates around the center of mass [which is not well-known and leads to a novel, rotationally removable component of the derivative coupling that we will call electron rotation factors below, cf. Eq. (96)]. The present findings should be helpful in the short term as far as interpreting surface hopping calculations for singlet systems (without spin) and then developing the new surface hopping algorithm in the long term for systems where one cannot ignore the electronic orbital and/or spin angular momentum. [ABSTRACT FROM AUTHOR]

The application of nitrification inhibitors (nitrapyrin) and urease inhibitors (N-(N-butyl) thiophosphoric triamide) under conventional water resources has been considered as an effective means to improve nitrogen utilization efficiency and mitigate soil greenhouse gas emissions. However, it is not known whether the inhibitors still have an inhibitory effect under unconventional water resources (reclaimed water and livestock wastewater) irrigation and whether their use in combination with biochar improves the mitigation effect. Therefore, unconventional water resources were used for irrigation, with groundwater (GW) control. Nitrapyrin and N-(N-butyl) thiophosphoric triamide were used alone or in combination with biochar in a pot experiment, and CO 2 , N 2 O, and CH 4 emissions were measured. The results showed that irrigation of unconventional water resources exacerbated global warming potential (GWP). All exogenous substance treatments increased CO 2 and CH 4 emissions and suppressed N 2 O emissions, independent of the type of water, compared to no substances (NS). The inhibitors were ineffective in reducing the GWP whether or not in combination with biochar, and the combined application of inhibitors with biochar further increased the GWP. This study suggests that using inhibitors and biochar in combination to regulate the greenhouse effect under unconventional water resources irrigation should be done with caution. [Display omitted] • Reclaimed water and livestock wastewater irrigation increased direct GWP. • Biochar did not hold water in the soil as expected. • Co-application of inhibitors and biochar failed to reduce GWP. • Inhibitors reduced N 2 O emissions while promoting CO 2 emissions. [ABSTRACT FROM AUTHOR]

Pseudomonas plecoglossicida is a Gram-negative bacterium that causes chronic granulomatous diseases in fish. However, the molecular mechanisms underlying its pathogenicity are poorly understood. Here, we identified a novel two-component system (TCS) named PvgAS in P. plecoglossicida , which regulates the expression of genes including the type VI secretion system-1 (T6SS-1), a key virulence factor, as well as the type III secretion system (T3SS) gene cluster and several genes associated with metabolic pathways. We showed that PvgAS is essential for bacterial virulence in large yellow croaker (LYC), an important aquaculture species, by controlling T6SS-1 expression, which is crucial for tissue colonization and intracellular survival. In contrast, T3SS was dispensable for P. plecoglossicida virulence in this model. We also confirmed T6SS-1 gene regulation by PvgAS at the transcriptional and translational levels using RNA-seq, RT-qPCR, lacZ reporter, and western blot assays. Our study reveals a regulatory and functional role of PvgAS in P. plecoglossicida pathogenicity and suggests that PvgAS may be a potential target for new therapeutic interventions against this bacterium. • Identified a novel two-component system PvgAS in Pseudomonas plecoglossicida. • PvgAS regulates type III and type VI secretion systems and bacterial virulence. • T3SS is dispensable but T6SS-1 is essential for P. plecoglossicida pathogenicity. • PvgAS is a potential target for developing new therapeutic interventions. [ABSTRACT FROM AUTHOR]

In this article, we are concerned with the Galerkin spectral approximation of an H 1 -norm state-constrained optimal control problem governed by a fourth-order partial differential equation (PDE). In the investigations, the optimality conditions for both the original control problem and its spectral approximation problem are, respectively, established, which are helpful to analyze the solution property of the spectral approximation problem. A priori and a posteriori error estimates of the spectral approximation problem are, therewith, built in detail. Finally, two numerical examples are carried out to validate the theoretical analysis. [ABSTRACT FROM AUTHOR]

This article describes the feedback control system in magnetic confinement devices, aiming to mitigate magnetohydrodynamic (MHD) instabilities and optimize plasma confinement within the Keda Torus eXperiment (KTX). The system includes saddle sensors as the input signal, a real-time control system as the core controller, a digital power amplifier (DPA) array as the actuator, and saddle coils as the brake to restrain the MHD instabilities. A flexible, distributed real-time control system based on field-programmable gate array (FPGA) has been developed and implemented for MHD control in KTX. This is the first time FPGA has been used to verify presupposed magnetic field mode, perform data acquisition, real-time calculation, and real-time feedback in KTX. It fulfills the real-time requirements of the experiment completely. The system is presently utilized in MHD control experiments, successfully achieving experiments at the current stage that reach the limit of Ohmic discharge, with good reproducibility. • A novel, flexible, and distributed real-time MHD feedback control was successfully implemented in the Keda Torus eXperiment (KTX). • A FPGA-based real-time system with a feedback frequency of 25 kHz and a total delay of less than 50 μ s was constructed. • The real-time control system effectively suppressed plasma instabilities, significantly extended plasma discharge duration to triple the shell time of KTX. [ABSTRACT FROM AUTHOR]

In this paper, the repeated low velocity impact responses and compression‐after‐impact (CAI) behaviors of woven glass fiber‐reinforced composite laminates were studied at the same total impact energy. Three types of impact energies, 30, 40, and 60 J, were chosen for the repeated impact tests relative to the single 120 J impact event. The impact behaviors including impact contact force–displacement and energy–time curves during the impact testing were recorded. The variations of the impact mechanical characteristics such as peak impact force, maximum displacement, and energy absorption were evaluated. The methods of visual inspection and stereo microscope were applied to identify the damage morphology of the impacted laminates. The damage accumulation was evaluated employing the absorbed energy fraction and normalized maximum displacement. It was found that the influences of impact energy on the repeated impact mechanical response are more remarkable than that of the impact number, and the impact events with fewer impact numbers cause more damage to the laminates for the same accumulative impact energy. Furthermore, the load–displacement and the CAI strength versus impact number curves were compared for the CAI testing. The ultimate load and the resulted CAI strength decrease with the increase of impact number owing to the influence of damage accumulation in repeated impacts. Highlights: Repeated impact responses were studied at the same total impact energy.The impact energy makes significant influence on the impact dynamic responses.The impact events with fewer impact numbers cause more damage to the composites.The CAI behavior was explored considering the effect of damage accumulation.The CAI strength of damaged laminates decreases with impact number increasing. [ABSTRACT FROM AUTHOR]

We develop a locally conservative, finite element method for the simulation of two-phase flow on quadrilateral meshes that minimize the number of degrees of freedom (DoFs) subject to accuracy requirements and the DoF continuity constraints. We use a mixed finite element method (MFEM) for the flow problem and an enriched Galerkin method (EG) for the transport, stabilized with an entropy viscosity. Standard elements for MFEM lose accuracy on quadrilaterals, so we use the newly developed AC elements which have our desired properties. Standard tensor product spaces used in EG have many excess DoFs, so we would like to use the minimal DoF serendipity elements. However, the standard elements lose accuracy on quadrilaterals, so we use the newly developed direct serendipity elements. We use the Hoteit-Firoozabadi formulation, which requires a capillary flux. We compute this in a novel way that does not break down when one of the saturations degenerate to its residual value. Extension to three dimensions is described. Numerical tests show that accurate results are obtained. [ABSTRACT FROM AUTHOR]

The nuclear–electronic orbital (NEO) method is a well-established approach for treating nuclei quantum mechanically in molecular systems beyond the usual Born–Oppenheimer approximation. In this work, we present a strategy to implement the NEO method for periodic electronic structure calculations, particularly focused on multicomponent density functional theory (DFT). The NEO-DFT method is implemented in an all-electron electronic structure code, FHI-aims, using a combination of analytical and numerical integration techniques as well as a resolution of the identity scheme to enhance computational efficiency. After validating this implementation, proof-of-concept applications are presented to illustrate the effects of quantized protons on the physical properties of extended systems, such as two-dimensional materials and liquid–semiconductor interfaces. Specifically, periodic NEO-DFT calculations are performed for a trans-polyacetylene chain, a hydrogen boride sheet, and a titanium oxide–water interface. The zero-point energy effects of the protons as well as electron–proton correlation are shown to noticeably impact the density of states and band structures for these systems. These developments provide a foundation for the application of multicomponent DFT to a wide range of other extended condensed matter systems. [ABSTRACT FROM AUTHOR]

Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). We have generated mice that carry Credependent knock-in alleles of U2af1(S34F), the murine version of the most common mutant allele of U2AF1 encountered in human cancers. Cre-mediated recombination inmurine hematopoietic lineages caused changes in RNA splicing, as well as multilineage cytopenia, macrocytic anemia, decreased hematopoietic stem and progenitor cells, lowgrade dysplasias, and impaired transplantability, but without lifespan shortening or leukemia development. In an attempt to identify U2af1(S34F)-cooperating changes that promote leukemogenesis, we combined U2af1(S34F) with Runx1 deficiency in mice and further treated the mice with a mutagen, N-ethyl-N-nitrosourea (ENU). Overall, 3 of 16 ENU-treated compound transgenic mice developed AML. However, AML did not arise in mice with other genotypes or without ENU treatment. Sequencing DNA from the three AMLs revealed somatic mutations homologous to those considered to be drivers of human AML, including predicted loss- or gain-of-function mutations in Tet2, Gata2, Idh1, and Ikzf1. However, the engineered U2af1(S34F) missense mutation reverted to WT in two of the three AML cases, implying that U2af1(S34F) is dispensable, or even selected against, once leukemia is established. [ABSTRACT FROM AUTHOR]

The housekeeping gene encoding β-actin appears to be the most widely-used internal reference for gene expression studies in experimental animals or their cell lines. However, the effectiveness of β-actin to normalize mRNA levels expression in many crustacean species is still object of debate. To date, it is still unclear if β-actin is suitable to be utilized as the internal reference in qualitative real-time gene expression study in crab species. To address this concern, we evaluated 5 candidate reference genes encoding β-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin A, elongation factor 1-α (EF1-α), and 18 S ribosomal RNA (18 S rRNA) in the swimming crabs ( Portunus trituberculatu s) models. Our data showed that the β-actin gene expression varied significantly across individual swimming crab individuals in gills or hemocytes and the expression of 18 S rRNA, EF1-α, cyclophilin or GAPDH gene were relatively stable compared to that of β-actin. Moreover, the expression stability of the reference genes among different tissues in normal crabs or after WSSV challenge was also tested by geNorm and NormFinder software. Among tissues, 18 S rRNA was most stably expressed in different tissues, followed by cyclophilin A and EF1-α, compared to β-actin and GAPDH. Upon to viral simulation, GAPDH was found to be the most stable internal control gene in gills and cyclophilin A was ranked as the most stable gene in hemocytes. [ABSTRACT FROM AUTHOR]

Background/Aims: Radiotherapy is the standard treatment option for advanced prostate cancer. Unfortunately, despite significant advances in radiation delivery, prostate cancer radioresistance occurs in a large proportion of patients undergoing radiotherapy. As a way to enhance radiotherapy effectiveness, research advances into the mechanisms regulating the immune response have revived interest in combination radiation and immune-based therapies. Methods: miR-195/-16 family and PD-L1 levels were analyzed in samples from a GSE21032 data set. Kaplan-Meier analysis was used to evaluate the difference in biochemical recurrence-free survival associated with miR-195 and miR-16 expression. qRT-PCR and western blot were used to evaluate the miR-195, miR-16 and PD-L1 expression. Then, we used bioinformatics analysis and luciferase reporter assay to predict and confirm the miR-195 and miR-16 target gene. Finally, we elucidate the miR-195 and miR-16 function on immune evasion in the DU145/T cell co-culture model and syngeneic mouse model treated with radiotion through qRT-PCR, western blot, Flow cytometry and ELISA. Results: High levels of miR-195 and miR-16 were positively correlated with the biochemical recurrence-free survival of prostate cancer patients. miR-195 and miR-16 were inversely correlated with PD-L1, PD-1, CD80 and CTLA-4 expression. Further mechanistic investigations revealed that miR-195 and miR-16 inhibited PD-L1 expression. Additionally, restoration of miR-195 and miR-16 expression enhanced radiotherapy via T cell activation in the tumor microenvironment by blocking PD-L1 expression. This synergistic effect of immunotherapy and radiotherapy was associated with the proliferation of functional cytotoxic CD8+ T cells and inhibition of myeloid-derived suppressor cells and regulatory T cells. Conclusions: Our data revealbiological and functional interactions between immunotherapy and radiotherapy through the miR-195/-16 family regulatory cascade. [ABSTRACT FROM AUTHOR]

In the summer of 2015, a disease outbreak occurred in the Silver pomfret ( Pampus argenteus ) that reared in indoor tanks of one farm in Eastern China. The primary external sign of affected fish was hemorrhages in fins. In the present study, Gram-negative rods were found in internal organs of diseased fish, and bacterial isolates obtained were identified as Photobacterium damselae subsp. damselae based on phenotypic and genetic analysis. Pathogenicity of one representative P. damselae subsp. damselae isolate was confirmed with experimental infections using healthy silver pomfret. This bacterial isolate also exhibited high cytotoxicity to against a marine finfish kidney cell line. In summary, P. damselae subsp. damselae was the causative agent of the disease outbreak of 2015 in aquacultured sliver pomfret. [ABSTRACT FROM AUTHOR]

Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in the pathogenesis of this leukemia. Recently, it was shown that chromodomain helicase DNA-binding protein-7 (CHD7) interacts with RUNX1 and suppresses RUNX1-induced expansion of hematopoietic stem and progenitor cells. These results suggest that CHD7 is also critical for CBFB-MYH11--induced leukemogenesis. To test this hypothesis, we generated Chd7f/fMx1-CreCbfb+/56M mice, which expressed the Cbfb-MYH11 fusion gene and deactivated Chd7 in hematopoietic cells upon inducing Cre with polyinosinicpolycytidylic acid. The Lin--Sca1--c-Kit1 (LK) population was significantly lower in Chd7f/fMx1-CreCbfb+/56M mice than in Mx1-CreCbfb+/56M mice. In addition, there were fewer 5-bromo-29-deoxyuridine--positive cells in the LKpopulation in Chd7f/fMx1-CreCbfb+/56M mice, and genes associated with cell cycle, cell growth, and proliferation were differentially expressed between Chd7f/fMx1-CreCbfb+/56M and Mx1-CreCbfb+/56M leukemic cells. In vitro studies showed that CHD7 interacted with CBFb-SMMHC through RUNX1 and that CHD7 enhanced transcriptional activity of RUNX1 and CBFβ-SMMHC on Csf1r, a RUNX1 target gene. Moreover, RNA sequencing of c-Kit1 cells showed that CHD7 functions mostly through altering the expression of RUNX1 target genes. Most importantly, Chd7 deficiency delayed Cbfb-MYH11--induced leukemia in both primary and transplanted mice. These data indicate that Chd7 is important for Cbfb-MYH11--induced leukemogenesis by facilitating RUNX1 regulation of transcription and cellular proliferation. [ABSTRACT FROM AUTHOR]

The continent–ocean transfer of dissolved silica (DSi, formed as SiO 2 ) via rivers constitutes an important part of the global silica cycle. The uptake of terrestrial vegetation and riverine phytoplankton are the key process controlling DSi migration within the drainage basin. Anthropogenic activities (including land use change and damming) have been altering DSi export by changing biological uptakes in the basin. A significant artificial lake effect of damming was exhibited on the spatial variations of chlorophyll-a (Chl.a) and DSi, which caused 15.39% of riverine DSi to be detained in the reservoir region of Changhuajiang River basin, Hainan Island, China. The biological uptake of terrestrial vegetation was behindhand responsible for seasonal fluctuations of DSi. The DSi uptake yields ranged from 19.44 t/km 2 /yr to 86.76 t/km 2 /yr during the different terrestrial vegetation types in the basin, in turn, tropical rainforest > crops > artificial economic forests > grassland. The try calculating of the DSi yield released by the silicates weathering was carried out taking biological processes in the basin into account. Taking into the plants uptake within the basin consideration, the corrected DSi yield from the silicates weathering was 18.6 t/km 2 /yr. Accordingly, the silicates weathering rate was up to 41.55 t/km 2 /yr, which was 1.36 times higher than that (30.39 t/km 2 /yr) without consideration of the biological uptake, and close to the fastest weathering rate of the granite basin (Puerto Rico) in the earth surface. Of the DSi released by the silicates weathering, 28.56% was absorbed by terrestrial vegetation, and 31.43% was consumed by riverine phytoplankton, and the rest was drainaged into the South China Sea. [ABSTRACT FROM AUTHOR]

This paper describes the complete design process of a passive prosthetic foot manufactured of Polylactic acid (PLA). It focuses on the reduction in the weight of prosthetic feet. Most of the prosthetic feet are designed with more weight and material than required. The structure of this passive prosthetic foot is designed and optimized as light as possible by using topology optimization. The topology-optimized model is printed from a Three-dimensional (3D) printer directly rather than interpreting the model using a Computer-aided design (CAD) software. The finite element analysis and the experiments are conducted to validate the structure. The test equipment is designed and installed for simulating the boundary conditions of the Heel strike (HS) and Toe off (TO). Since the weight of the prosthetic directly affects the mobility of patients, the weight of the proposed model is reduced 62 % when compared initial model to the final model. [ABSTRACT FROM AUTHOR]

[Objective] This study aimed to investigate the protective effects of proteins, salts, sugars and trace elements on soybean rhizobium strain HW-05 by response surface methodology. [Method] Different types, combinations, ratios and concentrations of protective agents were designed. Under simulated conditions, the optima protective agent formulation was screened for improving the survival rate a d survival time of soybean rhizobium strain HW-05. The optimal combination of significant factors was determined by Box-Behnken central composite design. [Result] Three significant factors afecting effective number of viable cells were screened, including peptone, xanthan gum and NaCl. The final concentration of each compound was optimized : 0. 13% peptone, 0. 011% xanthan gum, 0. 30% NaCl. [Conclusion] After addition of protective agent and preservation at room temperature for six months, effective number of viable cehs of soybean rhizobium strain HW-05 reached 3.185 X 10s CFU/ml. The survival rate of HW-05 ceHs was improved by more than 25% compared with the control group (2.458 X 10s CFU/ml). [ABSTRACT FROM AUTHOR]

The recently developed real-time nuclear–electronic orbital (RT-NEO) approach provides an elegant framework for treating electrons and selected nuclei, typically protons, quantum mechanically in nonequilibrium dynamical processes. However, the RT-NEO approach neglects the motion of the other nuclei, preventing a complete description of the coupled nuclear–electronic dynamics and spectroscopy. In this work, the dynamical interactions between the other nuclei and the electron–proton subsystem are described with the mixed quantum–classical Ehrenfest dynamics method. The NEO-Ehrenfest approach propagates the electrons and quantum protons in a time-dependent variational framework, while the remaining nuclei move classically on the corresponding average electron–proton vibronic surface. This approach includes the non-Born–Oppenheimer effects between the electrons and the quantum protons with RT-NEO and between the classical nuclei and the electron–proton subsystem with Ehrenfest dynamics. Spectral features for vibrational modes involving both quantum and classical nuclei are resolved from the time-dependent dipole moments. This work shows that the NEO-Ehrenfest method is a powerful tool to study dynamical processes with coupled electronic and nuclear degrees of freedom. [ABSTRACT FROM AUTHOR]

MicroRNA-99a (miR-99a) has been reported to function as a tumor suppressor through regulating cell cycle and apoptosis. But its clinical significance in ischemic stroke and its function in cerebral ischemia–reperfusion (I/R) injury remained unknown. Herein transient middle cerebral artery occlusion was built on C57BL/6 mice, followed by intracerebroventricular injection of miR-99a agomir or antagomir before reperfusion for 24 h. Our clinical analysis indicates that plasma miR-99a level was significantly decreased in ischemic stroke patients as compared to healthy subjects, and a significant correlation was observed between miR-99a and clinical parameters. And miR-99a overexpression mitigated I/R injury in mice, as evidenced by reduced brain infarct volume and neural apoptosis, whereas miR-99a downregulation aggravates brain injury. In vitro, miR-99a protected neuro-2a cells against hydrogen peroxide-induced oxidative stress injury, by improving cell viability, suppressing LDH release and cell apoptosis. In addition, miR-99a overexpression inhibited H 2 O 2 induced G1/S phase transition in neuro-2a cells, accompanied by a significant decrease in cyclin D1 level and a tendency of down-regulation of CDK6. It was further proved in mice that miR-99a inhibited cyclin D1 and CDK6 expressions following cerebral I/R injury. These findings indicate that miR-99a reduces neuronal damage following cerebral I/R through regulating cell cycle progression and preventing apoptosis, suggesting that miR-99a could be used as a new therapeutic agent targeting neuronal cell cycle re-entry following stroke. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the potential role of miR-23a-3p in experimental brain ischemia-reperfusion injury. Cerebral ischemia reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 1 h in C57/BL6 mice. And miR-23a-3p angomir was transfected to upregulate the miR-23a-3p level. Our results showed that miR-23a-3p levels were transiently increased at 4 h after reperfusion in the peri-infarction area, while markedly increased in the infarction core at reperfusion 4 h and 24 h. Importantly, in vivo study demonstrated that miR-23a-3p angomir treatment through intracerebroventricular injection markedly decreased cerebral infarction volume after MCAO. Simultaneously, miR-23a-3p reduced peroxidative production nitric oxide (NO) and 3-nitrotyrosine (3-NT), and increased the expression of manganese superoxide dismutase (MnSOD). In vitro study demonstrated that miR-23a-3p decreased hydrogen peroxide (H 2 O 2 )-induced lactate dehydrogenase (LDH) leakage dose-dependently, and reduced protein levels of activated caspase-3 in neuro-2a cells. In addition, miR-23a-3p reduced H 2 O 2 -induced production of NO and 3-NT dose-dependently, and reversed the decreased activity of total SOD and MnSOD in neuro-2a cells. Our study indicated that miR-23a-3p suppressed oxidative stress and lessened cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Skin microbiota of Gulf of Mexico fishes were investigated by ribosomal internal spacer analysis ( RISA) and 16 S r RNA gene sequencing. A total of 102 fish specimens representing six species ( Mugil cephalus, Lutjanus campechanus, Cynoscion nebulosus, Cynoscion arenarius, Micropogonias undulatus, and Lagodon rhomboides) were sampled at regular intervals throughout a year. The skin microbiota from each individual fish was analyzed by RISA and produced complex profiles with 23 bands on average. Similarities between RISA profiles ranged from 97.5% to 4.0%. At 70% similarity, 11 clusters were defined, each grouping individuals from the same fish species. Multidimensional scaling and analysis of similarity correlated the RISA-defined clusters with geographic locality, date, and fish species. Global R values indicated that fish species was the most indicative variable for group separation. Analysis of 16 S rRNA gene sequences (from pooled samples of 10 individual fish for each fish species) showed that the Proteobacteria was the predominant phylum in skin microbiota, followed by the Firmicutes and the Actinobacteria. The distribution and abundance of bacterial sequences were different among all species analyzed. Aeribacillus was found in all fish species representing 19% of all clones sequenced, while some genera were fish species-specific ( Neorickettsia in M. cephalus and Microbacterium in L. campechanus). Our data provide evidence for the existence of specific skin microbiota associated with particular fish species. [ABSTRACT FROM AUTHOR]

Effects of austempering temperature on the microstructure, crystallographic characteristics, mechanical properties and damping capacity of a low-carbon bainitic steel were investigated in the present study. The results showed that a decrease in the austempering temperature from 380 to 320 °C led to an increase in both the fractions of bainitic ferrite and retained austenite, especially those with filmy morphology. Meanwhile, the thickness of bainitic ferrite laths was refined and the carbon concentration of retained austenite was increased, thereby significantly improving the yield strength, impact toughness and total elongation. Moreover, the variant selection effect became less important with decreasing austempering temperature, so that variants changed from belonging to the same Bain groups with low-angle grain boundaries to sharing the same parallel relation of close-packed groups with high-angle grain boundaries, which is an effective way to increase the impact toughness. The density of dislocation and the amounts of bainitic ferrite and retained austenite are the significant factors that enhance the damping capacity of austempered steel. An outstanding combination of both mechanical properties and damping capacity (925 ± 10 MPa yield strength, 1440 ± 2 MPa tensile strength, total elongation of 12.8 ± 0.4%, and V-notch unit impact toughness at 20 and − 40 °C of 56 ± 3 and 31 ± 2 J/cm2, as well as the maximum logarithmic decrement coefficient of 0.1164, respectively) was achieved by austempering at 320 °C. [ABSTRACT FROM AUTHOR]

Objectives: YKL-40 has been demonstrated to be related to atherosclerosis, but its role in predicting plaque status and the outcome of carotid atherosclerosis (CAS) caused by CagA-positive helicobacter pylori remains unclear. This study was aimed to investigate the role of YKL-40 in predicting the outcome of carotid atherosclerosis with CagA-positive Helicobacter pylori infection. Methods: The serum concentrations of YKL-40, C-reaction protein in 310 patients undergoing color Duplex assessment of carotid atherosclerosis were recorded and divided into 3 groups according to the infectious statuses of helicobacter pylori. We also examined serum YKL-40, C-reaction protein and the plaque morphology in animal model of carotid atherosclerosis with different types of helicobacter pylori infection. Results: Overexpression of YKL-40 was only found in carotid atherosclerosis group with CagA-positive helicobacter pylori infection; C-reaction protein failed to distinguish different infectious statuses of helicobacter pylori infection. In patients with CagA-positive helicobacter pylori infection, elevated YKL-40 expression was accompanied by more severe clinical symptoms. We also confirmed similar findings in rabbit model of carotid atherosclerosis with CagA-positive helicobacter pylori infection. We found that in 7 rabbits treated with anti-helicobacter pylori therapy, the serum YKL-40 level decreased and the plaque became more stable. Conclusion: Our findings suggested that increased serum YKL-40 level indicates plaque instability and more severe clinical symptoms of carotid atherosclerosis with CagA-positive helicobacter pylori infection. Compared with C-reaction protein, YKL-40 seems to be a more specific predictor of plaque status and outcome of carotid atherosclerosis with CagA-positive helicobacter pylori infection. [ABSTRACT FROM AUTHOR]

Multicomponent quantum chemistry allows the quantum mechanical treatment of electrons and specified protons on the same level. Typically the goal is to identify a self-consistent-field (SCF) solution that is the global minimum associated with the molecular orbital coefficients of the underlying Hartree-Fock (HF) or density functional theory (DFT) calculation. To determine whether the solution is a minimum or a saddle point, herein we derive the stability conditions for multicomponent HF and DFT in the nuclear-electronic orbital (NEO) framework. The gradient is always zero for an SCF solution, whereas the Hessian must be positive semi-definite for the solution to be a minimum rather than a saddle point. The stability matrices for NEO-HF and NEO-DFT have the same matrix structures, which are identical to the working matrices of their corresponding linear response time-dependent theories (NEO-TDHF and NEO-TDDFT) but with a different metric. A negative eigenvalue of the stability matrix is a necessary but not sufficient condition for the corresponding NEO-TDHF or NEO-TDDFT working equation to have an imaginary eigenvalue solution. Electron-proton systems could potentially exhibit three types of instabilities: electronic, protonic, and electron-proton vibronic instabilities. The internal and external stabilities for theories with different constraints on the spin and spatial orbitals can be analyzed. This stability analysis is a useful tool for characterizing SCF solutions and is helpful when searching for lower-energy solutions. Initial applications to HCN, HNC, and 2-cyanomalonaldehyde, in conjunction with NEO ∆SCF calculations, highlight possible connections between stationary points in nuclear coordinate space for conventional electronic structure calculations and stationary points in orbital space for NEO calculations. [ABSTRACT FROM AUTHOR]

Floral transition in Arabidopsis is tightly controlled by complex genetic regulatory networks in response to endogenous and environmental flowering signals. SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and SHORT VEGETATIVE PHASE (SVP), two key MADS-domain transcription factors, perceive these signals and function as antagonistic flowering regulators. To understand how these factors mediate floral transition, we mapped in vivo binding sites of SOC1 and SVP using chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays (ChIP-chip). Genes that encoded proteins with transcription regulator activity and transcription factor activity were the most enriched groups of genes of those bound by SOC1 and SVP, which indicates their central roles in flowering regulatory networks. In combination with gene expression microarray studies, we further identified the genes whose expression was controlled directly by SOC1 or SVP. Among the common direct targets identified, APETALA2 ( AP2)-like genes that repress FT and SOC1 expression were down-regulated by SOC1, but up-regulated by SVP, revealing a complex feedback regulation among the key genes that determine the integration of flowering signals. SOC1 regulatory regions were also accessed by SOC1 itself and SVP, suggesting that self-activation and repression by SVP contribute to the control of SOC1 expression. In addition, ChIP-chip analysis demonstrated that miR156e and miR172a, which are involved in the regulation of AP2-like genes, were direct targets of SOC1 and SVP, respectively. Taken together, these findings revealed that feedback regulatory loops mediated by SOC1 and SVP are essential components of the gene regulatory networks that underpin the integration of flowering signals during floral transition. [ABSTRACT FROM AUTHOR]

The fluvial geochemistry of the mainstream and tributaries of the Zengjiang River was investigated, and the mass balance approach and deduction methods were used to estimate the uptake of atmospheric CO through rock chemical weathering. The results showed that the chemical runoff mainly consisted of HCO, Ca, Na, and dissolved Si, and that silicate mineral weathering was significant, but carbonate mineral weathering was a minor source of dissolved loads in the Zengjiang River basin because of the low amount of interlayered carbonate rock strata in the catchment. The ion composition indicated that atmospheric CO was the primary erosive agent for rock chemical weathering in the Zengjiang River basin. The CO consumption fluxes caused by rock chemical weathering were (3.50-3.81) × 10 mol km a, which is just lower than that in tropical and subtropical basalt and carbonate regions, and is much higher than that in temperate and cold-temperate regions, indicating that surficial chemical weathering processes in the humid and hot monsoon current influencing the low-middle latitude zone of the Northern Hemisphere constitutes a significant carbon sink in the global biogeochemical cycle. [ABSTRACT FROM AUTHOR]

Abstract: Monthly samples of riverine water were collected and analyzed for the concentrations of major ions (Ca2+, Mg2+, K+, Na+, HCO3 −, SO4 2−, Cl−, NO3 −), dissolved silicon, and total dissolved solids (TDS) at Wuzhou hydrological station located between the middle and lower reaches of the Xijiang River (XJR) from March 2005 to April 2006. More frequent sampling and analysis were carried out during the catastrophic flooding in June 2005. Stoichiometric analysis was applied for tracing sources of major ions and estimating CO2 consumption from the chemical weathering of rocks. The results demonstrate that the chemical weathering of carbonate and silicate rocks within the drainage basin is the main source of the dissolved chemical substances in the XJR. Some 81.20% of the riverine cations originated from the chemical weathering processes induced by carbonic acid, 11.32% by sulfuric acid, and the other 7.48% from the dissolution of gypsum and precipitates of sea salts within the drainage basin. The CO2 flux consumed by the rock chemical weathering within the XJR basin is 2.37×1011 mol y−1, of which 0.64×1011 mol y−1 results from silicate rock chemical weathering, and 1.73×1011 mol y−1 results from carbonate rock chemical weathering. The CO2 consumption comprises 0.38×1011 mol during the 9-d catastrophic flooding. The CO2 consumption from rock chemical weathering in humid subtropical zones regulates atmospheric CO2 level and constitutes a significant part of the global carbon budget. The carbon sink potential of rock chemical weathering processes in the humid subtropical zones deserves extra attention. [Copyright &y& Elsevier]

The excitatory amino acid carrier EAAC1 belongs to a family of glutamate transporters that use the electrochemical transmembrane gradients of sodium and potassium to mediate uphill transport of glutamate into the cell. While the sites of cation interaction with EAAC1 are unknown, two cation binding sites were observed in the crystal structure of the bacterial glutamate transporter homologue GltPh. Although occupied by Tl[sup+] in the crystal structure, these sites were proposed to be Na[sup+] binding sites. Thereibre, we tested whether Tl[sup+] has the ability to replace Na[sup+] also in the mammalian transporters. Our data demonstrate that Tl[sup+] can bind to EAAC1 with high affinity and mediate a host of different functions. TP[sup+] can functionally replace potassium when applied to the cytoplasm and can support glutamate transport current. When applied extracellularly, TP[sup+] induces some behavior that mimics that of the Na[sup+]-bound transporter, such as activation of the cation-induced anion conductance and creation of a substrate binding site, but it cannot replace Na[sup+] in supporting glutamate transport current. Moreover, our data show a differential effect of mutations to two acidic amino acids potentially involved in cation binding (D367 and D454) on Na[sup+] and Tl[sup+] affinity. Overall, our results demonstrate that the ability of the glutamate transporters to interact with Tl[sup+] is conserved between GltPh and a mammalian member of the transporter family. However, in contrast to GltPh, which does not bind K[sup+], Tl[sup+] is more efficient in mimicking K[sup+] than Na[sup+] when interacting with the mammalian protein. [ABSTRACT FROM AUTHOR]

Osteosarcomas account for about 20% of all primary bone neoplasms, and affect predominantly adolescents. Important prognostic factors include the presence or absence of metastases at the time of presentation and tumor response to neoadjuvant chemotherapy. Biological markers predicting metastases and chemoresistance are not well characterized. cDNA microarray analysis enables one to examine the expression of thousands of genes in tumor samples. We performed cDNA microarray analysis of histologically low and high grade areas in osteosarcomas to identify gene expression patterns which may depict aggressive behavior. Microarray analysis with 1.2 K cancer array revealed many differentially expressed genes (both upregulated and downregulated), in histologically high grade tumor samples as compared with a low grade sample. Selected up and down regulated markers in the high grade sarcomas were tested in a group of high grade osteosarcomnas (OS) with varying responses to chemotherapy. Of the multiple markers analyzed, ezrin, a member of the ERM family of membrane-cytoskeleton linkers showed an expression pattern statistically significant between tumors with good response to chemotherapy compared with tumors with poor response (p = 0.036). We discuss our findings, with current review of literature. [ABSTRACT FROM AUTHOR]

Transmembrane glutamate transport by the excitatory amino acid carrier (EAAC1) is coupled to the cotransport of three Na+ ions and one proton. Previously, we suggested that the mechanism of H+ cotransport involves protonation of the conserved glutamate residue E373. However, it was also speculated that the cotransported proton is shared in a W-binding network, possibly involving the conserved histidine 295 in the sixth transmembrane domain of EAAC1. Here, we used site-directed mutagenesis together with pre-steady-state electrophysiological analysis of the mutant transporters to test the protonation state of H295 and to determine its involvement in proton transport by EAAC1. Our results show that replacement of H295 with glutamine, an amino acid residue that cannot be protonated, generates a fully functional transporter with transport kinetics that are close to those of the wild-type EAAC1. In contrast, replacement with lysine results in a transporter in which substrate binding and translocation are dramatically inhibited. Furthermore, it is demonstrated that the effect of the histidine 295 to lysine mutation on the glutamate affinity is caused by its positive charge, since wild-type-like affinity can be restored by changing the extracellular pH to 10.0, thus partially deprotonating H295K. Together, these results suggest that histidine 295 is not protonated in EAAC1 at physiological pH and, thus, does not contribute to H+ cotransport. This conclusion is supported by data from H295C-E373C double mutant transporters which demonstrate that these residues cannot be linked by oxidation, indicating that H295 and E373 are not close in space and do not form a proton binding network. A kinetic scheme is used to quantify the results, which includes binding of the cotransported proton to E373 and binding of a modulatory, nontransported proton to the amino acid side chain in position 295. [ABSTRACT FROM AUTHOR]

The phenomenon of dedifferentiation typically occurs in soft tissue sarcomas where a low grade or well-differentiated tumor shows an abrupt transformation to a high-grade sarcoma without lineage specificity. The biological behavior and metastatic potential of these tumors is dictated by the dedifferentiated phenotype. Tumor material was available from two dedifferentiated liposarcomas. We performed cDNA microarray analysis of a dedifferentiated liposarcoma in which the atypical lipomatous/well-differentiated and dedifferentiated portions were grossly distinct, to find differentially expressed genes in the dedifferentiated component compared to the well-differentiated component. There were 100 differentially expressed genes, both up- and down-regulated in the high grade sarcoma. In addition, we performed RT-PCR on selected genes in both cases to confirm the microarray findings. We discuss the expression patterns of these genes in comparison to other studies in the literature. [ABSTRACT FROM AUTHOR]

We previously found that male mice with myocardial infarction (MI) had a high rate of cardiac rupture, which generally occurred at 3 to 5 days after MI. Since matrix metalloproteinases (MMPs) play an important role in infarct healing, tissue repair and extracellular matrix (ECM) remodeling post-MI, we studied the temporal relationship of MMP expression and inflammatory response to cardiac rupture after acute MI. Male C57BL/6J mice were subjected to MI (induced by ligating the left anterior descending coronary artery) and killed 1, 2, 4, 7 or 14 days after MI. MMP-2 and MMP-9 activity in the heart were measured by zymography. Collagen content was measured by hydroxyproline assay. We found that after MI, MMP-9 activity increased as early as 1 day and reached a maximum by 2-4 days, associated with a similar increase in neutrophil and macrophage infiltration in the infarct area. MMP-2 started to increase rapidly within 4 days, reaching a maximum by 7 days and remaining high even at 14 days. Intense macrophage infiltration appeared by 4 days after MI and then gradually decreased within 7 to 14 days. Collagen content was unchanged until 4 days after MI, at which point it increased and remained high thereafter. Our data suggest that in mice, overexpression of MMP-2 and MMP-9 (possibly expressed mainly by neutrophils and macrophages) may lead to excessive ECM degradation in the early phase of MI, impairing infarct healing and aggravating early remodeling which in turn causes cardiac rupture. [Copyright &y& Elsevier]

Based on the author’s research results on high-speed travelling type of double four-rod spatial parallel mechanism in new type virtual axis machine tools with combined architecture, this paper lays emphasis on the problems of singularity analysis and singularity loci calculation of such mechanism. In theory, it has found out three kinds of singularity loci of the mechanism by utilizing an identification matrix that is constructed on the conception of screw, and revealed the relationship between the structural parameter b and the singularity loci, thus laid a theoretical foundation for optimizing the parameter of the mechanism. In aspect of application, by applying the result in the design of new five-coordinate virtual axis machine tool with combined architecture, it has effectively solved the affection of singularity, greatly increased the working space of the machine tool and achieved good effect. [Copyright &y& Elsevier]

Discusses the detection of exogenous genes in genetically modified plants with multiplex polymerase chain reaction (MPCR). Significance of the development of plant genetic engineering to scientists; Types of genetically modified tobacco; Classification of transgene sequences of exogenous DNA fragments; Uses of MPCR.

Simple Summary: In this paper, a three-round nested PCR assay with high specificity and sensitivity (2.62 copies/reaction), employing the Pseudomonas plecoglossicida sctU gene, was established. The detection system was used to detect large yellow croaker samples in the Zhejiang and Fujian areas. It was found that March and April were the peak times of visceral white nodules disease, which was inversely related to temperature. Using this detection method, early detection of visceral white nodules disease in large yellow croakers could be realized. The visceral white nodules disease in the internal organs of Larimichthys crocea has caused significant harm in the aquaculture of this species, with Pseudomonas plecoglossicida considered one of the core pathogens causing this disease. In this study, we designed three pairs of specific nested PCR primers targeting the sctU gene of P. plecoglossicida, a crucial component of the Type III secretion system (T3SS), which is instrumental in bacterial pathogenesis and virulence. Through the optimization of PCR reaction conditions, specificity testing, and sensitivity determination, a method was established for the accurate detection of P. plecoglossicida. This method yielded single amplification products, exhibited a false positive rate of zero for reference bacteria, and achieved a detection sensitivity of a minimum of 2.62 copies/reaction for the target sequence. Using the detection method, we conducted analyses on the diseased populations of L. crocea, involving a total of 64 screened fishes along the southeast coast of China from 2021 to 2023. The results revealed that the infection rate of P. plecoglossicida in diseased L. crocea exceeded over 90% in March and April, while in other months, the maximum recorded infection rate was merely 10%. The detection method developed in this study shows potential for early warning and routine monitoring of visceral white nodules disease in the internal organs of species such as L. crocea. [ABSTRACT FROM AUTHOR]

Refracturing treatment is widely used to enhance the well productivity in shale gas reservoirs, particularly for initially fractured wells with low productivity. The principal of this work is based on the transient behavior of pressure and rate for a vertically refractured well in a shale gas reservoir, considering the fracture reorientation and adsorption and desorption property. Based on the point-source theory and Laplace transform, a semi-analytical solution for a refractured well is obtained by coupling the point-source solution of a shale gas reservoir and the solution of artificial fractures. The validation of this new solution is carried out smoothly by comparison with the results from the commercial software COMSOL. Five typical flow regimes are identified on the transient pressure curve, namely bi-linear flow regime, formation linear flow regime, mid-radial flow regime, inter-porosity flow regime, and pseudo-radial flow regime. A groove segment occurs on the transient-pressure derivative curve, and its width and depth largely depend on the adsorption and desorption constant and storativity ratio. Due to fracture reorientation, bi-linear flow regime, formation linear flow regime, and mid-radial flow regime may be significantly impacted. In addition, the transient rate of the refractured well in a shale gas reservoir is positively proportional to the storativity ratio, inter-porosity coefficient, and adsorption and desorption constant, while it is inversely proportional to fracture reorientation. These results provide important references for parameter design, property inversion, and productivity prediction of refracturing treatment in shale gas reservoirs. [ABSTRACT FROM AUTHOR]