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In this work, a novel multiscale topology optimization method has been proposed for the design of electromechanical energy-harvesting systems converting mechanical vibrations into electric currents made of non-piezoelectric materials. At the microscopic scale, the material is assumed to be periodic, porous, and flexoelectric, although not piezoelectric. A first step of topology optimization is performed, in order to maximize the effective (homogenized) flexoelectric properties of the material, where a flexoelectric homogenization model is first formulated. As a result, the effective material, although made of a non-piezoelectric material, has apparent piezoelectric properties. In a second step, these properties are used to model the behavior of a dynamic electromechanical energy-harvesting system structure. A second topology optimization step, this time performed at the structural scale, aims to maximize the system electromechanical coupling factor (ECF) for a given forced vibration frequency, including the micro-inertial effect. At both scales, an isogeometric analysis method is employed to solve the strain-gradient problems numerically. We show that the optimized structure obtained offers significant gains in terms of ECF (by a factor of between 2 and 20) compared with non-optimized structures of the same volume, over a wide range of excitation frequencies. The procedure could open up new possibilities in the design of energy recovery systems without the use of piezoelectric materials. [ABSTRACT FROM AUTHOR]

Consideration of transient effects is important for industrial applications of heat transfer structure optimisation studies; however, the huge computational cost associated with transient problems is a pressing concern. This paper proposes an extension of a previous reduced-dimensional model to transient conjugate heat transfer between a fluid flow and solid-heated plates in a plate heat exchanger. The extended reduced-dimensional model introduces the temperature field of the plate governed by the heat conduction equation, which is coupled to the temperature field of the fluid, governed by the convection-diffusion equation, through the heat flux balance equation at the contact surface. The model is based on assumptions of fully developed flow and constant temperature profile, reducing the three-dimensional problem to a planar problem and significantly reducing computational costs. The accuracy of the model for the simulation of transient heat transfer is verified by comparison with a three-dimensional model. In this paper, the topography of the heat exchanger plate is optimised for both steady-state and transient conditions by applying the reduced-dimensional model. The effectiveness of the optimised design was demonstrated by the cross-check of both the reduced-dimensional and full three-dimensional models. Furthermore, this work considers the effect of time-independent boundary conditions and time-dependent boundary conditions on transient optimisation. The transient and steady-state optimised designs are analysed and compared for both conditions, and the necessity of transient optimisation is discussed. [ABSTRACT FROM AUTHOR]

A novel procedure has emerged in recent years within oilfields - namely, the utilization of a hybrid fracturing method employing pre-CO2 injection along with sand-carry slick water. In this paper, based on the real logging data of shale oil reservoirs in the second member of Cangdong Sag, Huanghua Depression, combined with the GOHFER, a coupled 3-D hydraulic fracture propagation model is proposed. This research delves into an examination of how engineering factors exert their influence on the process of fracture propagation. The quantitative analysis is conducted encompassing critical fracture parameters such as half-length, height, and width, and self-defined fracture seepage area and fracture front fractal dimension. The research findings indicate that as injection displacement increases, the fracture shape undergoes a transformation from being "long, low, and wide" to becoming "short, high, and narrow". [ABSTRACT FROM AUTHOR]

The biological properties of red wine are attributed to potent antioxidants and the antiradical activity of polyphenols. Recently, it has been noted that metal ions can substantially alter the reactivity of polyphenols. In this study, we observed that the radical scavenging activity of red wine increases when Cu(II), an exemplar of transition metal ions, is either removed or chelated. However, Conversely, the elimination of alkaline earth metal ions such as Mg(II) and Ca(II), representing main group elements, has negligible impact on this activity. We explored the interactions between Cu(II), Mg(II), and Ca(II) with three most abundant phenolic substances –gallic acid, catechin, and caffeic acid – and analyzed the corresponding radical scavenging kinetics in a uniform buffer solution at pH 7.2. Cu(II) formed 1 : 1 complexes with these three polyphenols, substantially diminishing their inherent radical scavenging potential. In accordance with the effect in red wine, Ca(II) and Mg(II) displayed no significant influence on the radical scavenging kinetics of these three polyphenols within the buffer solution. Our findings suggest that the removal of Cu(II), and potentially other transition metal ions, during the wine production process could enhance the antioxidant activity of red wine. [ABSTRACT FROM AUTHOR]

This paper proposes a reduced-dimensional model for the structural optimisation of conjugate heat transfer between parallel plates with constant temperature and a fluid channel of varying height. The model considers heat conduction and convection through a planar reduced-dimensional version of the convection-diffusion equation. To significantly reduce the computational time for the optimisation process, assumptions on the through-thickness velocity and temperature fields are made, allowing to transform a three-dimensional problem to a two-dimensional one. The accuracy and limitations of the model are investigated through an in-depth parametric analysis and are seen to be acceptable in the context of optimisation when considering the reduced computational cost. To allow for the optimisation of varying topology and topography, the local channel height is linearly interpolated based on the design field. The height parametrisation combined with the reduced-dimensional model provides physical meaning to intermediate design variables and removes the traditional requirement of 0–1 discrete solutions for topology optimisation. This allows the free switch between topology and topography optimisation, but it is illustrated through various examples that only topography changes are relevant for the treated problems. Two optimisation examples, a square heat exchanger and a manifold heat exchanger, demonstrate that the reduced-dimensional model is sufficiently accurate to be applied to structural optimisation. In comparison with shape optimisation using a full three-dimensional model, it is demonstrated that topography optimisation using the reduced-dimensional model can achieve equivalent optimised designs at a significantly lower computational cost. [ABSTRACT FROM AUTHOR]

The article "Fast and slow lanes of the vagus" discusses symposium reports presented at the International Society of Autonomic Neuroscience Congress in Australia. It focuses on the fast and slow functions of the cardiac vagus nerve, exploring cutting-edge technologies and new knowledge in this field. The symposium highlights the potential therapeutic benefits of manipulating the vagus nerve in cardiovascular diseases and complements ongoing research trials in this area. [Extracted from the article]

As is well acknowledged that mechanical properties of material extrusion (ME) additive manufacturing polymers are highly related to processing parameters. Meanwhile, the yield strength is one of the key properties of a material, which critically affects a component's manufacturing and further application. To reveal the effect of printing parameters such as layer thickness, printing speed and deposition orientation on the yield strength of ME polymers without extensive experimental researches, a novel, integrated prediction model accounting for processing-structure-property relationship is put forward. In this model, processing related representative volume element (RVE) of unidirectional ME polymers is firstly estimated by combining the volume conservation method and thermal-sintering model. Next, assuming raw polymers to be homogenous, isotropic, and ideal elastic-plastic, a multiscale approach integrating Hill model and homogenization theory is presented to acquire the stress-strain curves of anisotropic ME polymers under externally applied loadings. In this procedure, the dependence of RVE's estimated anisotropic parameters in Hill model on their external loading states is paid attention. By this means, the three-dimensional yield behavior of ME polymers, including the off-axis yield strength, can be obtained. The validity of the proposed method is examined by comparing with existing test data in literature or our measured ones. Finally, explicit discussions are made. Many valuable conclusions are drawn, which may be of unique significance for the future processing optimization and quality improvement of final products. [ABSTRACT FROM AUTHOR]

A numerical procedure based on isogeometric analysis (IGA) is developed to analyze the dynamic response of flexoelectric systems in the frequency domain. In materials or composites with an effective flexoelectric response, a polarization can be induced by local strain gradients. In general, these effects are small in the static regime. However, larger effects may be induced by dynamic loads, and can be used in energy harvesters converting mechanical vibrations into electrical energy. In this work, the equations describing frequency response of flexoelectric systems under dynamic loads are first described. Then, an IGA discretization procedure is employed to handle the C 1 continuity of the displacement fields. The conditions of both open and close-circuits are formulated. The numerical methodology is used to evaluate the sensitivity of different parameters such as load resistors, dynamic scale parameter, and the use of flexoelectric or non-flexoelectric materials on the frequency response of output voltage, power and displacements of beam-like structures, possibly incorporating structural geometrical features. The potential of IGA with respect to mesh refinement (h-refinement) and higher order approximation (p-refinement) for modeling complex geometries within the present framework is invetigated. [ABSTRACT FROM AUTHOR]

The increased interlayer spacing and vanadium vacancies enhance the diffusivity of Zn2+ ions in V d -NVO, endowing it with excellent cyclic stability and a capacity retention of 81.76 % after 1000 cycles at 5 A g−1. [Display omitted] • Pre-removing some ammonium ions from NH 4 V 4 O 10 expands the interlayer spacing. • The vanadium vacancy accelerates the diffusion kinetics of Zn2+. • The V d -NVO electrode demonstrates a reversible capacity of 131 mAh g−1 even after 1000 cycles at 5 A g−1. Ammonium vanadate (NH 4 V 4 O 10) is regarded as a promising cathode material for aqueous zinc-ion batteries, given its considerable theoretical capacity and tunable interlayer spacing. However, due to its inherent low electrical conductivity and the excessive presence of ammonium ions between layers, NH 4 V 4 O 10 exhibits unsatisfactory electrochemical performance. In this study, it is proposed that the electrochemical performance of NH 4 V 4 O 10 can be significantly enhanced by removing part of the ammonium cation and increasing the vanadium vacancy. The decrease of ammonium further increases the layer spacing, reduces the irreversible deamination and accelerates the diffusion of Zn2+. Density functional theory (DFT) calculations reveal that increasing vanadium vacancies significantly diminishes the strong electrostatic interactions between the V-O layers and Zn2+, enhances the material's electrical conductivity, and stabilizes the crystal structure during zinc ion (de)intercalation, thus obtaining excellent electrochemical properties. As a result, the V d -NVO cathode demonstrates a high reversible capacity of 371 mAh g−1, excellent rate performance, and remarkable cyclic stability, maintaining a reversible capacity of 131 mAh g−1 even after 1000 cycles at 5 A g−1. [ABSTRACT FROM AUTHOR]

• A new multi-material topology optimization for designing ultra-wide band gap phononic crystals is proposed. • An adjustable stair form model is integrated with floating projection constraints to avoid parameter dependencies. • Four-material phononic crystals are generated to improve band gap performance which can rival Au/Epoxy systems. • Simultaneously considering the effect of mass and cost constraints. The multi-material phononic crystals (PnCs) not only has the potential to achieve broadband vibration reduction and noise control, but also has the capability to reduce costs and weight. This paper proposes a single variable based topological optimization method for widening the band gaps (BGs) in multi-material PnCs. The method combines the floating projection topology optimization (FPTO) method, and utilizes an adjustable stair form interpolation model is used to construct a mapping from a single design variable field to a multi-material field. It avoids the nested form of overlap between different materials to characterize multiple material phases, and the parameter self adaptability of FPTO solves the problem of multiple parameters in univariate optimization methods. Floating projection constraint is used to improve the projection strategy for intermediate densities to obtain a 0/1 design, resulting in a final design with a clear topological structure. Optimized PnCs using various engineered materials are generated to improve BG performance which can rival Au/Epoxy systems. And the effects of mass and cost constraints is also considered to achieve multi-material PnCs by maximizing the BG. The results also indicate that the resulting multi-material PnCs may achieve ultra-wide BG characteristics. [ABSTRACT FROM AUTHOR]

We study a stochastic control/stopping problem with a series of inequality-type and equality-type expectation constraints in a general non-Markovian framework. We demonstrate that the stochastic control/stopping problem with expectation constraints (CSEC) is independent of a specific probability setting and is equivalent to the constrained stochastic control/stopping problem in weak formulation (an optimization over joint laws of Brownian motion, state dynamics, diffusion controls and stopping rules on an enlarged canonical space). Using a martingale-problem formulation of controlled SDEs in spirit of Stroock and Varadhan (2006), we characterize the probability classes in weak formulation by countably many actions of canonical processes, and thus obtain the upper semi-analyticity of the CSEC value function. Then we employ a measurable selection argument to establish a dynamic programming principle (DPP) in weak formulation for the CSEC value function, in which the conditional expected costs act as additional states for constraint levels at the intermediate horizon. This article extends (El Karoui and Tan, 2013) to the expectation-constraint case. We extend our previous work (Bayraktar and Yao, 2024) to the more complicated setting where the diffusion is controlled. Compared to that paper the topological properties of diffusion-control spaces and the corresponding measurability are more technically involved which complicate the arguments especially for the measurable selection for the super-solution side of DPP in the weak formulation. [ABSTRACT FROM AUTHOR]

• The pre-intercalated Co2+ is used as an interlayer "pillar" ion to effectively enhance the structural stability. • The replacement of ammonium ions with Co2+ serves to reduce the irreversible deammoniation process. • The conductivity of ammonium vanadate is enhanced by the pre-intercalated of Co2+. Ammonium vanadium (NH 4 V 4 O 10) emerges as a highly promising cathode material for aqueous zinc ion batteries due to its open crystal structure and high theoretical capacity. Unfortunately, the slow intercalation dynamics of the zinc ions and the structural instability are limiting factors for further development. Herein, it is proposed that Co2+ is pre-inserted into the NH 4 V 4 O 10 interlayer to replace some of the ammonium ions. It not only reduces irreversible deamination but also improves the structural stability as an interlayer column ion, thus increasing the electrochemical activity of NH 4 V 4 O 10. The NH₄V₄O 10 electrode doped with cobalt is capable of achieving a specific discharge capacity of up to 394.11 mAh/g at 0.1 A/g. Following 3000 cycles at 10 A/g, a discharge capacity of 103.61 mAh/g is retained, with a capacity retention rate of 92.1 %. [ABSTRACT FROM AUTHOR]

We propose a novel nonlinear topology optimization framework tailored for flexoelectric soft dielectrics undergoing large deformation. A numerical method based on Isogeometric analysis (IGA) is introduced to nonlinear soft dielectrics at finite strain, ensuring the C 1 -continuity for flexoelectric problems. We outline the process of consistent linearizations and IGA discretizations. Additionally, we introduce an innovative and efficient Strain Density Function (SDF) interpolation scheme for optimizing electromechanical coupling factors (ECFs). In this scheme, the interpolation of electromechanical and hyper-elastic energy terms is grounded in the SIMP model, while a linear material interpolation model is employed for the dielectric energy. Our numerical analysis highlights the remarkable performance of the proposed SDF interpolation scheme in nonlinear electromechanical optimization scenarios. An energy remedy scheme is applied to void regions to eliminate the instability of nonlinear optimization, effectively preventing distortion deformations in low-stiffness elements. Furthermore, we investigate the influence of size effect and larger deformation on the optimization of flexoelectric soft materials. The proposed topology optimization framework adeptly leverages the interplay between size effect and larger deformation, resulting in a notable improvement in ECFs within the optimized structures. Finally, the electromechanical coupling factors (ECFs) of the optimized structures in all the examined cases exhibit enhancements up to 9 times as compared to the reference guess designs. [ABSTRACT FROM AUTHOR]

Breast cancer is a serious malignancy with a high incidence worldwide and a tendency to relapse. We used integrated bioinformatics analysis to identify potential biomarkers in breast carcinoma in the present study. Microarray data, 127breast tumor samples and 23 non-tumor samples, received from the Gene Expression Omnibus (GEO) dataset; 121 differentially expressed genes (DEGs) were selected. Functional analysis using DAVID revealed that these DEGs were highly gathered in endodermal cell differentiation and proteinaceous extracellular matrix. Five bioactive compounds (prostaglandin J2, tanespimycin, semustine, 5182598, and flunarizine) were identified using Connectivity Map. We used Cytoscape software and STRING dataset to structure a protein-protein interaction (PPI) network. The expression of CD24, MMP1, SDC1, and SPP1 was much higher in breast carcinoma tissue than in Para cancerous tissues analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and ONCOMINE. Overexpression of CD24, MMP1, SDC1, and SPP1 indicated the poor prognosis in breast carcinoma patients analyzed by Kaplan-Meier (KM) Plotter. Immunohistochemistry microarray was used to further confirm that protein expression of CD24, MMP1, SDC1, and SPP1 was much higher in tumor sections than in Para cancerous tissues. Hub genes expression at the protein level was correlated tothe breast cancer subtype and grade. Furthermore, immunity analysis showed that CD24, MMP1, SDC1, and SPP1 were potentially associated with five immune cell types infiltration (CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells) by TIMER. Thus, this study indicates potential biomarkers that could have applications in the development of immune therapy for breast cancer. However, further studies are required for verifying these results in vivo and vitro. [ABSTRACT FROM AUTHOR]

A deep-learning approach is proposed to predict an optimized high-resolution structure with multi-boundary conditions. An enhanced deep super-resolution (SR) neural network and a convolutional neural network are constructed and trained to establish the mapping relationship between low- and high-resolution structures for the topology optimization problem. The data set for training and testing is generated using the solid isotropic material with penalization method, in which the training and test sets have different geometric boundary conditions. Each sample contains both low- and high-resolution structures. The deep neural network is trained with limited training samples (4000), and numerical experiments demonstrate that the proposed method can obtain an accurate high-resolution structure in negligible computational time. Moreover, the proposed method has the generalization ability necessary to predict high-resolution structures with multi-geometric boundary conditions. The effective incorporation of a deep SR neural network and topology optimization has enormous potential for future practical applications in large-scale structural design. [ABSTRACT FROM AUTHOR]

Background: Blacks tend to have a stronger inflammatory immune response than Whites. We hypothesized that racial differences in host immunity also manifest in the tumor microenvironment, constituting part of a distinct aggressive tumor biology underlying higher mortality in Black women.Methods: Pathological and gene expression profiling approaches were used for characterizing infiltrating immune cells in breast tumor microenvironment from 1315 patients from the Women's Circle of Health Study. Racial differences in tumor immune phenotypes were compared, with results validated in a publicly accessible dataset. Prognostic associations of immune phenotypes were assessed in 3 independent cohorts.Results: We found marked and consistent differences in tumor immune responses between Black and White patients. Not only did tumors from Blacks display a stronger overall immune presence but also the composition and quality of immune infiltrates differed, regardless of tumor subtypes. Black patients had a stronger CD4+ and B-cell response, and further, a more exhausted CD8+ T-cell profile. A signature indicating a higher ratio of exhausted CD8+ T cells to total CD8+ T cells (ExCD8-r) was consistently associated with poorer survival, particularly among hormone receptor-positive patients. Among hormone receptor-negative patients, combinations of the absolute fraction of CD8+ T cells and ExCD8-r signature identified the CD8lowExCD8-rhigh subgroup, the most prevalent among Blacks, with the worst survival.Conclusions: Our findings of a distinct exhausted CD8+ T-cell signature in Black breast cancer patients indicate an immunobiological basis for their more aggressive disease and a rationale for the use of immune checkpoint inhibitors targeting the exhaustion phenotype. [ABSTRACT FROM AUTHOR]

To address the limitations of databases in the field of emotion recognition and to cater to the trend of integrating data from multiple sources, we have established a multi-modal emotional dataset based on spontaneous expression of drivers. By selecting emotional induction materials and inducing emotions before each driving task, facial expression videos and synchronous physiological signals of the drivers during driving were collected. The dataset includes records of 64 participants under five different emotions (neutral, happy, angry, sad, and fear), and the emotional valence, arousal, and peak time of all participants in each driving task were recorded. To analyze the dataset, spatio-temporal convolutional neural networks were designed to analyze the different modalities of data with varying durations in the dataset, aiming to investigate their performance in emotion recognition. The results demonstrate that the fusion of multi-modal data significantly improves the accuracy of driver's emotion recognition, with accuracy increases of 11.28% and 6.83% compared to using only facial video signals or physiological signals, respectively. Therefore, the publication and analysis of multi-modal emotional data for driving scenarios is crucial to support further research in the fields of multimodal perception and intelligent transportation engineering. • Established materials and framework for driver emotion data collection. • Established multi-modal dataset for driver emotions with effective analysis. • Designed an effective spatio-temporal neural network for data analysis. • Explored emotion recognition performance across modalities and time windows. • Multi-modal recognition exceeds single-modal by 11.28% and 6.83% accuracy. [ABSTRACT FROM AUTHOR]

The Jiaonan uplift and its adjacent areas (JUAA) are the result of collision and amalgamation of the North China plate and Yangtze plate. In this area, the tectonic environment is complex and crustal deformation is strong. However, detailed and in-depth study of the upper crustal structure and medium properties in the JUAA has not previously been performed. The high-resolution three-dimensional crustal velocity structure of the JUAA is helpful to analyze the characteristics of the crustal structure in this area and is important for evaluating the tectonic environment and medium properties of the JUAA. We obtained the three-dimensional crustal velocity structure in the JUAA using the double-difference seismic tomography technique, and found that the Rizhao area and the sea areas to its southwest in the Jiaonan uplift are characterized by a high-velocity structure, and that most of the high-velocity anomaly area is located in the sea area. The crustal velocity values of the southern end of the Yishu fault zone are also high. The high crustal velocity anomaly areas in the JUAA are considered to be caused by the upwelling of mantle material. The velocity structure of the upper crust beneath the depression structures shows notable low-velocity anomalies, which are closely related to loose sediments in the depression structures. The existence of abnormally high-velocity and low-velocity structures in the Jiaonan uplift indicates that there are substantial differences in the properties of the crustal media in the Jiaonan uplift. Crust-mantle interaction in the Jiaonan uplift is mainly concentrated in the Rizhao area and sea areas to its southwest. [ABSTRACT FROM AUTHOR]

A new topology optimization procedure based on the extended finite element method (XFEM) for enhancing the fracture strength of structural specific position is proposed. The XFEM is used as an approach for the description of discontinuity states in the design domain, such as cracks, voids and inclusions, by employing the enrichment shape function with discontinuous properties. Based on linear elastic fracture mechanics and the bi-directional evolutionary structural optimization (BESO) method, the J integral, as a criterion for predicting crack growth, is considered to prevent crack propagation and enhance the fracture strength of the structure. Several typical examples are provided to verify the effectiveness of the present method by considering different situations of length and location of the crack, and the interactions between crack, void and inclusion. The results suggest that combining the XFEM with BESO is a promising approach for optimizing the anti-fracturing mechanical properties of structures. [ABSTRACT FROM AUTHOR]

The article reports that nitrogen (N)-induced lattice contraction generally increase the hydrogen evolution catalysis of phosphorus (P)-rich transition metal phosphides (TMPs). Topics discussed include the impact of the N-P strong interaction on the atomic wave function, the use of lattice engineering for band structure tuning and the effects of N dopants on the electronic structures of CoP2.

Statin has been proposed to have a capacity to reduce the risk of pancreatic cancer, while the obtained results are not consistent. To gain a clearer picture of the relationship between statin use and pancreatic cancer, the present meta-analysis took into consideration data from eight cohort studies, ten case-control studies and three RCTs. We searched all relevant studies on the effect of statin use on the risk of pancreatic cancer using PubMed, Embase and the Cochrane library database from inception to July 30, 2018. The following search terms were used: (1) statin ("statins", "statin", "3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors", "atorvastatin", "cerivastatin", "fluvastatin", "lovastatin", "pravastatin", "rosuvastatin", "simvastatin"); (2) pancreatic cancer ("cancer", "neoplasm", "malignancy"). We manually examined the references of the relevant articles and reviews to identify additional studies. A total of 21 studies, published between 2001 and July 2018 and involving 1 148 680 cases and 2 177 842 controls, fulfilled the selection criteria. The pooled results revealed a significant relationship between statin use and pancreatic cancer risk (OR = 0.84, 95% CI 0.72-0.98, P = 0.000, I² = 84.3%). However, lipophilic statins (OR = 1.07, 95% CI 0.97-1.18, P = 0.651, I² = 0.0%) had no significant effect on the risk of pancreatic cancer. In contrast, short -term statin use (OR = 0.72, 95% CI 0.54-0.96, P = 0.000, I² = 80.1%) and long-term statin use (OR = 0.70, 95% CI 0.54-0.92, P = 0.000, I² = 79.8%) significantly reduced pancreatic cancer risk. Notably, the high heterogeneity among the selected studies was eliminated by excluding the three studies that focused on restricted populations. Statin could significantly reduce the risk of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Through evolutionary processes, helicoidal structures have been proven to exhibit exceptional load‐carrying capacity and impact resistance performance. To date, extensive experimental and numerical studies have been carried out on their impact behaviors, while few relevant analytical studies have been reported even though it is urgently needed for the preliminary assessment of structure design and optimization. In this work, based on the first shear deformation theory (FSDT) and the improved linearized Hertzian contact method, an analytical model for low velocity impact (LVI) performances of helicoidal laminates with arbitrary layups is developed. Therein, the post‐impact damage is taken into account according to continuum damage mechanics (CDM). Comparisons of load‐carrying capacity and energy‐absorbed performance between the proposed model prediction and the existing experimental data\numerical results have been made for verification. Besides, LVI behaviors of conventional laminates with unidirectional distribution andcross‐ply arrangement are discussed. Moreover, the role of rotation angle, impact velocity and the plate dimension on helicoidal laminates' LVI performances are analyzed quantitatively. There is evidence that helical layouts are better able to absorb energy and delay the in‐plane damage. Highlights: The LVI responses of bio‐inspired single‐helicoidal (SH) and double‐helicoidal (DH) composite laminate are studied.An effective model to predict the LVI responses considered the post‐impact damage is developed.A comparison of the LVI performance of single‐helicoidal structures with various lay‐up schemes is carried out.DH structure has better low velocity impact resistance than SH structure when the rotation angle shares the same. [ABSTRACT FROM AUTHOR]

Integrated production and distribution scheduling are important problems in a manufacturing system, distribution system, and system collaborative optimization. Under the carbon emission policy, managers must aim to reduce carbon emissions in manufacturing and distribution. This research considers an integrated single-machine scheduling and multi-vehicle routing problem, which allows the switching of machine in a period between two adjacent workpieces. Initially, a mathematical programming model is established to minimize the total carbon emissions, and then a tabu search hybrid algorithm is proposed to solve the minimization problem. Moreover, an enterprise case and twenty simulated examples are studied. Computational results verify the advantage of integrated scheduling model and show that a sustainable scheduling method can reduce the total carbon emissions by coordinating production and distribution effectively. Finally, the model is extended to the cases of minimizing total costs and minimizing both total costs and carbon emissions. The model and algorithm can guide the green manufacturing and logistics for industrial enterprises. • An integrated single-machine scheduling and multi-vehicle routing problem. • The aim is to minimize the total carbon emissions. • A tabu search hybrid Algorithm embedding the exact method of machine scheduling. • The model and Algorithm are verified by an industrial and some simulated examples. [ABSTRACT FROM AUTHOR]

Young black women are at higher risk of triple‐negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein‐truncating mutations at the exome‐wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early‐onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome‐wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing. [ABSTRACT FROM AUTHOR]

Given p∈(1,2], the wellposedness of backward stochastic differential equations with jumps (BSDEJs) in Lp sense gives rise to a so-called g-expectation with Lp domain under the jump filtration (the one generated by a Brownian motion and a Poisson random measure). In this paper, we extend such a g-expectation to a nonlinear expectation E with Lp domain that is consistent with the jump filtration. We study the basic (martingale) properties of the jump-filtration consistent nonlinear expectation E and show that under certain domination condition, the nonlinear expectation E can be represented by some g-expectation. [ABSTRACT FROM AUTHOR]

This article proposes a new algorithm for topological optimization under dynamic loading which combines cellular automata with bi-directional evolutionary structural optimization (BESO). The local rules of cellular automata are used to update the design variables, which avoids the difficulty of obtaining gradient information under nonlinear collision conditions. The intermediate-density design problem of hybrid cellular automata is solved using the BESO concept of 0-1 binary discrete variables. Some improvement strategies are also proposed for the hybrid algorithm to solve certain problems in nonlinear topological optimization, e.g. numerical oscillation. Some typical examples of crashworthiness problems are provided to illustrate the efficiency of the proposed method and its ability to find the final optimal solution. Finally, numerical results obtained using the proposed algorithms are compared with reference examples taken from the literature. The results show that the hybrid method is computationally efficient and stable. [ABSTRACT FROM AUTHOR]

• Platform encroaches on retail if it identifies a product with high sales potential. • Sales-, carbon-, and dual-signaling strategies are explored. • The choice of signaling strategy depends on market status. • Carbon signaling increases separating cost but decreases the environmental impact. Information asymmetry and e-commerce platform encroachment affect the production and sales strategies of manufacturers, wherein sales information is an effective signal to realize information disclosure. Meanwhile, the low-carbon characteristics of products provide manufacturers with an alternative signal option. We establish a dynamic signaling game model in which a manufacturer sells green products through a platform and the sales potential of the product is unknown to the platform in the first stage. The platform encroaches on the manufacturer with high sales potential (HM) in the second stage. This encroachment behavior prompts the HM to disguise itself as a manufacturer with low sales potential (LM) to evade platform encroachment, thereby aggravating information asymmetry. We explore the signals that the LM should use to separate itself from the HM more efficiently and the optimal low-carbon production strategies under three signaling strategies (i.e., sales, carbon, and dual signals). We reveal that the carbon signal gives the HM a stronger motivation to disguise itself than the sales signal, thereby increasing the LM's separating costs but decreasing the environmental impact. In addition, the LM should choose the sales signal in a high-quality market; in contrast, the dual (carbon) signal is optimal in a general (low-quality) market. Our results offer insights for green manufacturing and signal selection under information asymmetry and platform encroachment. [ABSTRACT FROM AUTHOR]

Selection pressure due to exposure to infectious pathogens endemic to Africa may explain distinct genetic variations in immune response genes. However, the impact of those genetic variations on human immunity remains understudied, especially within the context of modern lifestyles and living environments, which are drastically different from early humans in sub Saharan Africa. There are few data on population differences in constitutional immune environment, where genetic ancestry and environment are likely two primary sources of variation. In a study integrating genetic, molecular and epidemiologic data, we examined population differences in plasma levels of 14 cytokines involved in innate and adaptive immunity, including those implicated in chronic inflammation, and possible contributing factors to such differences, in 914 AA and 855 EA women. We observed significant differences in 7 cytokines, including higher plasma levels of CCL2, CCL11, IL4 and IL10 in EAs and higher levels of IL1RA and IFNα2 in AAs. Analyses of a wide range of demographic and lifestyle factors showed significant impact, with age, education level, obesity, smoking, and alcohol intake, accounting for some, but not all, observed population differences for the cytokines examined. Levels of two pro-inflammatory chemokines, CCL2 and CCL11, were strongly associated with percent of African ancestry among AAs. Through admixture mapping, the signal was pinpointed to local ancestry at 1q23, with fine-mapping analysis refined to the Duffy-null allele of rs2814778. In AA women, this variant was a major determinant of systemic levels of CCL2 (p = 1.1e-58) and CCL11 (p = 2.2e-110), accounting for 19% and 40% of the phenotypic variance, respectively. Our data reveal strong ancestral footprints in inflammatory chemokine regulation. The Duffy-null allele may indicate a loss of the buffering function for chemokine levels. The substantial immune differences by ancestry may have broad implications to health disparities between AA and EA populations. [ABSTRACT FROM AUTHOR]

When a train travels through a tunnel at high speed, obvious pressure transients are generated because of the restricted airspace within the tunnel, which have an impact on the comfort of passengers and the structural safety of the train and the tunnel. In this paper, by performing a series of field measurements for high-speed railway tunnels in China, the aerodynamic pressures at different test points in the tunnels were obtained; the formation mechanism of pressure, the distribution of amplitude and the attenuation of pressure were analyzed. The results show that after the train travelled out of the tunnel, the pressure continued to fluctuate according to a fixed cycle and the pressure amplitude decreased exponentially as the number of cycles increased. The attenuation coefficient of the pressure had nothing to do with the train speed, but was associated with the tunnel length, the position of test points and the holes of the tunnel hoods. [ABSTRACT FROM AUTHOR]

In this study, the behavior of multi-frusta configurations under axial loading was analyzed, the effect of column spacing, number of tubes, shells, and cone combinations investigated, and multi-objective optimization applied to obtain optimal multi-frusta configurations. The results obtained indicate that the interaction between multi-frusta configurations without shell improves the system's specific energy absorption (SEA), the SEA of multi-frusta tubes can be improved by the rigid outer shell, and the overall energy absorption of restricted size structures benefit from having an appropriate number of multi-frusta configurations. They also show that cross-arranged tapers offer better energy absorption characteristics than other arrangements. [ABSTRACT FROM AUTHOR]

Multi-cell metallic thin-walled tubes have gained wide popular in recent years, due to their significantly improvements in mechanical behaviors comparing with general single sample. In this investigation, some attempts to learn of the mechanism of folding process of multi-cell thin-walled square tubes were carried out. The half-wave length has been fully determined theoretically by the means of Super Folding Element. The relationship between the half-wave length as well as mean load versus cell amounts has been given. Afterwards, comprehensive numerical simulations were also conducted after necessary experimental validation, with the cell amounts range from 1 × 1 to 15 × 15 which have the equal weight but different thickness. Detailed evolutional process of deformation mode, half-wave length, and energy absorption capability were analyzed parametrically. The results turned out that the vital influence factor on mechanical properties of multi-cell tubes directly lies in the half-wave length caused by different cell amounts. With the increasing of cells, the half-wave length decreases while the energy absorption capability promotes. Evidently promotion can be observed compared with general single cell tube. All these achievements shed a light on disclosing the multi-cell effect on mechanical properties. [ABSTRACT FROM AUTHOR]

Givenp∈ (1, 2), the uniquesolutions of backward stochastic differential equations with jumps (BSDEJs) allow us to extend the notion ofg−evaluations, in particularg−expectations, to the jump case withdomains. We explore many important properties of the extendedg−evaluations, including optional sampling, upcrossing inequality, Doob-Meyer decomposition, generator representation, and Jensen's inequality. Most of these results are important for the further development of jump-filtration consistent nonlinear expectations withdomains in [95]. [ABSTRACT FROM PUBLISHER]

Given p ∈ ( 1 , 2 ) , we study L p solutions of a multi-dimensional backward stochastic differential equation with jumps (BSDEJ) whose generator may not be Lipschitz continuous in ( y , z ) -variables. We show that such a BSDEJ with p -integrable terminal data admits a unique L p solution by approximating the monotonic generator by a sequence of Lipschitz generators via convolution with mollifiers and using a stability result. [ABSTRACT FROM AUTHOR]

A strong edge-coloring of a graph is a proper edge-coloring where each color class induces a matching. We denote by χ′s (G) the strong chromatic index of G which is the smallest integer k such that G can be strongly edgecolored with k colors. It is known that every planar graph G has a strong edge-coloring with at most 4∆(G) + 4 colors [R.J. Faudree, A. Gyárfás, R.H. Schelp and Zs. Tuza, The strong chromatic index of graphs, Ars Combin. 29B (1990) 205-211]. In this paper, we show that if G is a planar graph with g ≥ 5, then χ′s (G) ≤ 4∆(G) - 2 when ∆(G) ≥ 6 and χ′s (G) ≤ 19 when ∆(G) = 5, where g is the girth of G. [ABSTRACT FROM AUTHOR]

We analyze an optimal stopping problem sup γ ∈ T E ¯ 0 [ Y γ ∧ τ 0 ] with random maturity τ 0 under a nonlinear expectation E ¯ 0 [ ⋅ ] : = sup P ∈ P E P [ ⋅ ] , where P is a weakly compact set of mutually singular probabilities. The maturity τ 0 is specified as the hitting time to level 0 of some continuous index process X at which the payoff process Y is even allowed to have a positive jump. When P collects a variety of semimartingale measures, the optimal stopping problem can be viewed as a discretionary stopping problem for a player who can influence both drift and volatility of the dynamic of underlying stochastic flow. We utilize a martingale approach to construct an optimal pair ( P ∗ , γ ∗ ) for sup ( P , γ ) ∈ P × T E P [ Y γ ∧ τ 0 ] , in which γ ∗ is the first time Y meets the limit Z of its approximating E ¯ − Snell envelopes. To overcome the technical subtleties caused by the mutual singularity of probabilities in P and the discontinuity of the payoff process Y , we approximate τ 0 by an increasing sequence of Lipschitz continuous stopping times and approximate Y by a sequence of uniformly continuous processes. [ABSTRACT FROM AUTHOR]

By using air as the superior oxidant, a highly atom-efficient synthesis of 2-substituted quinazolines is developed by a CsOH-mediated direct aerobic oxidative reaction of the readily available and stable 2-aminoarylmethanols and nitriles. Effectively working as the promoter in the alcohol oxidation, nitrile hydration, and cyclocondensation steps, CsOH is the best base for the reaction. A similar method can also be extended to the synthesis of substituted quinolines starting from methyl ketones instead of nitriles. [ABSTRACT FROM AUTHOR]

Source separation and treatment of human urine have been recognized as a resource-efficient alternative to conventional urban drainage, not only reducing nutrient loads on municipal wastewater treatment plants, but recovering valuable resources from waste streams. In this work, on-site phosphorus (P) recovery from real urine was carried out by using the brine from a reverse osmosis process as the flush water for urine-diverting toilets and a P precipitant, while nitrogen (N) was removed via short-cut nitrification-denitrification (SCND) in a membrane bioreactor (MBR). More than 90% of P was recovered by mixing the urine with reverse osmosis brine (1:1, v/v) under the condition of pH > 9.0. The recovered precipitates contained 10–15% of P and can potentially be reused for phosphate fertilizer production. Stable SCND was achieved in a MBR, and 45% of N was removed with the organic compounds in urine as the electron donor for denitrification. Methanol addition significantly elevated denitrification, which in turn replenished the alkalinity required for nitrification. More than 99% of P, 90% of organics and 90% of N were removed in the combined precipitation and MBR process. Nitrosomonas was observed to be the predominant ammonium-oxidizing bacteria, while nitrite-oxidizing bacteria (NOB) were absent in the microbial communities as revealed by fluorescence in situ hybridization and pyrosequencing technique. High concentrations of free ammonia and nitrite acids, as well as low dissolved oxygen, are the prevailing factors to inhibit the growth of NOB, which allows for stable operation of SCND in the MBR. [ABSTRACT FROM AUTHOR]

Water-soluble poly(vinyl alcohol) (PVA) nanofibers cannot be applied in aqueous condition. Fortunately, the PVA nanofibers can become stable in aqueous condition after physically or chemically crosslinked. However, these crosslinking methods require some harsh experimental conditions. In this article, organic solvents were introduced as the media to crosslink PVA nanofibers with glutaraldehyde, which is different from the conventional crosslinking method. The results of the field emission scanning electron microscopy (FESEM) show that the crosslinked PVA nanofibers can maintain the morphology not only in water but also in extreme solutions (such as hot water for 2 d, strong acid/alkaline solutions at 95 °C for 2 h). The tensile strength of the crosslinked PVA nanofiber mats can maintain more than 12.1 ± 1.1 MPa after soaked into these extreme solutions. The crosslinked PVA nanofiber mats with high stability and porous morphology have potential applications as filter membrane and adsorbing material. [ABSTRACT FROM AUTHOR]

• The combined AGA/IFPWEM optimization algorithm is proposed to efficiently design thin EMs plates with ultrawide FVBGs. • The effects of initial topologies and material volume fraction constraint on the unit cell optimization are explored. • The physical mechanisms including the iso-frequency contours, the phase, and group velocities are studied. • The flexural wave propagation in finite-size lattices composed of optimized unit cells is investigated numerically and experimentally. The properties of bandgaps (BGs) for manipulating elastic/acoustic waves are highly determined by the spatial distribution of materials in the primitive unit cell. In this work, the topological optimization strategy is implemented to design thin elastic metamaterial plates to broaden the total relative width of flexural vibration bandgaps (FVBGs). It is formulated based on the adaptive genetic algorithm (AGA) and solved using the improved fast plane wave expansion method (IFPWEM), which can contribute to improving the efficiency of optimization. The effects of initial designs and material volume fraction constraints on the optimization are discussed in detail. Based on the optimized solutions evolved from Initialization IV and volume fraction constraint f 0 = 0.25, the wave propagation (iso-frequency contours, the phase, and group velocities) is utilized to investigate the physical mechanisms. The numerical and experimental results of the finite-size lattices composed of optimized unit cells demonstrate that out-of-plane flexural waves can be transmitted or prohibited, which is in perfect match with the predicted results of band structures. Additionally, the present methodology is expected to explore their potential application in the vibration attenuation of the two-component thin elastic metamaterials plates. [Display omitted] [ABSTRACT FROM AUTHOR]

Major depressive disorder is a complex psychiatric disorder with a high prevalence rate worldwide. Previous studies have demonstrated the involvement of the prelimbic cortex (PL) in mediating depressive-like behavior, however, the exact molecular mechanism taking place in the PL remains unclear. In the present study, we conducted high-throughput sequencing of mRNAs and miRNAs in PL tissue harvested from chronic social defeat stress (CSDS) susceptible male mice. We identified 59 differentially expressed mRNAs and 6 differentially expressed miRNAs, in which 40 mRNAs and 3 miRNAs were up-regulated, while 19 mRNAs and 3 miRNAs were down-regulated. Integrated analysis of miRNA-mRNA networks suggested that GPR35 signaling might be involved in CSDS-induced depressive-like behaviors. RT-PCR and western blot assays validated that Abra, Sell and GPR35 were up-regulated. Functionally, inhibition of GPR35 in the PL ameliorated CSDS-induced depressive-like behaviors. Thus, the present study provided a global view of mRNA and miRNA profiles in the PL of male stress susceptible mice, and suggested that GPR35 signaling was associated with CSDS-induced depressive-like behaviors. These results may be valuable for further investigations of the molecular regulatory mechanisms in stress-induced depression. • CSDS induces depressive-like behavior. • CSDS activates the prelimbic cortex. • 59 mRNAs and 6 miRNAs were changed in the prelimbic cortex after CSDS. • GPR35 signaling may be involved in depressive-like behavior. [ABSTRACT FROM AUTHOR]

A micro-pressure wave (MPW) is generated when a train enters a tunnel at high speed, which causes a strong impact on the environment around the tunnel. The increased lining used to repair damage in high-speed railway tunnels changes cross-sections and has a strong influence on the MPW at the tunnel exit. In this paper, the methods of full-scale measurement, numerical simulation and moving-model experiments are used to study the MPW generated in a tunnel whose lining is increased. The rules governing the effect of increased linings on MPWs are obtained, which can be used as a reference for the Tunnel Damage Regulation Project in China. [ABSTRACT FROM AUTHOR]

We study a doubly reflected backward stochastic differential equation (BSDE) with integrable parameters and the related Dynkin game. When the lower obstacle L and the upper obstacle U of the equation are completely separated, we construct a unique solution of the doubly reflected BSDE by pasting local solutions, and show that the Y -component of the unique solution represents the value process of the corresponding Dynkin game under g -evaluation, a nonlinear expectation induced by BSDEs with the same generator g as the doubly reflected BSDE concerned. In particular, the first time τ ∗ when process Y meets L and the first time γ ∗ when process Y meets U form a saddle point of the Dynkin game. [ABSTRACT FROM AUTHOR]

• Elastic wave propagation of metamaterial plates with various lattices are studied with numerical and experimental methods. • The applicability of irreducible Brillouin zone is investigated through iso-frequency contours. • The broaden bandgaps are found by coupling Bragg scattering and local resonance bandgaps below 300 Hz. • The effect of the scatterer shapes and structural parameters of unit cells on the band structures is explored. Elastic wave propagation characteristics of elastic metamaterial plates embedded scatterer with various lattices are explored numerically and experimentally in this study, for the attenuation of in-plane longitudinal and out-of-plane flexural waves in the subwavelength frequency region. Firstly, the mathematical models of the elastic metamaterial plates are established, and the dispersion relations are derived by the plane wave expansion (PWE) method based on Bloch's theorem. Furthermore, the applicability of the irreducible Brillouin zone (IBZ) for different lattices is also investigated through iso-frequency contours. The analysis of the bandgap formation mechanism indicates that the proposed metamaterial plates can enlarge the bandgaps (BGs) in the low-frequency range by coupling Bragg and local resonance BGs. Moreover, the influences of the scatterer shapes, geometric and material parameters on the BGs are investigated, and which combination of parameters has positive significance for opening low-frequency broadband is also discussed. The results show that the vibration transmittance obtained by experiment and numerical calculation is in good agreement with the predicted results of band structures. Therefore, the elastic metamaterial plates should be promising in the application of low-frequency wave mitigation. [ABSTRACT FROM AUTHOR]

The periodontal ligament is a crucial tissue that provides support to the periodontium. Situated between the alveolar bone and the tooth root, it consists primarily of fibroblasts, cementoblasts, osteoblasts, osteoclasts, periodontal ligament stem cells (PDLSCs), and epithelial cell rests of Malassez. Fibroblasts, cementoblasts, osteoblasts, and osteoclasts are functionally differentiated cells, whereas PDLSCs are undifferentiated mesenchymal stem cells. The dynamic development of these cells is intricately linked to periodontal changes and homeostasis. Notably, the regulation of programmed cell death facilitates the clearance of necrotic tissue and plays a pivotal role in immune response. However, it also potentially contributes to the loss of periodontal supporting tissues and root resorption. These findings have significant implications for understanding the occurrence and progression of periodontitis, as well as the mechanisms underlying orthodontic root resorption. Further, the regulation of periodontal ligament cell (PDLC) death is influenced by both systemic and local factors. This comprehensive review focuses on recent studies reporting the mechanisms of PDLC death and related factors. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) signaling pathway in pulmonary fibrosis was investigated in cell and animal models. mTOR overactivation in alveolar epithelial cells (AECs) was achieved in the conditional and inducible Tsc1 knock-down mice SPC-rtTA/TetO-Cre/Tsc1fx/+ (STT). Doxycycline caused Tsc1 knock-down and consequently mTOR activation in AECs for the STT mice. Mice treated with bleomycin exhibited increased mortality and pulmonary fibrosis compared with control mice. In wild-type C57BL/6J mice, pretreatment with rapamycin attenuated the bleomycin-mediated mortality and fibrosis. Rapamycin-mediated mouse survival benefit was inhibited by chloroquine, an autophagy inhibitor. Autophagosomes were decreased in the lungs after bleomycin exposure. Rapamycin induced the production of autophagosomes and diminished p62. We concluded that mTOR overactivation in AECs and compromised autophagy in the lungs are involved in the pathogenesis of pulmonary fibrosis. The suppression of mTOR and enhancement of autophagy may be used for treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo. Wistar rats were administered with ATR at doses of 10, 50 and 100 mg/kg body weight by oral gavage for three months. In terms of histopathology, the expression of autophagy- and apoptosis-related genes as well as proteins related to the Beclin-1/B-cell lymphoma 2 (Bcl-2) autophagy and apoptosis pathways were examined in the rat nigrostriatal dopaminergic system. We observed degenerative micromorphology indicative of neuronal apoptosis and mitochondrial autophagy by electron microscopy in ATR-exposed rat striatum. The rat ventral mesencephalon in the ATR-exposed groups also showed increased expression of Beclin-1, LC3-II, Bax and Caspase-9, and decreased expression of tyrosine hydroxylase (TH), Bcl-xl and Bcl-2. These findings indicate that ATR may induce autophagy- and apoptosis-related changes in doparminergic neurons. Furthermore, this induction may be regulated by the Beclin-1 and Bcl-2 autophagy and apoptosis pathways, and this may help to better understand the mechanism underlying the neurotoxicity of ATR. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. Results We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. Conclusion The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression. [ABSTRACT FROM AUTHOR]

Following an immune challenge, there is two-way communication between the nervous and immune systems. It is proposed that a neural reflex-the inflammatory reflex-regulates the plasma levels of the key proinflammatory cytokine TNF-α, and that its efferent pathway is in the splanchnic sympathetic nerves. The evidence for this reflex is based on experiments on anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show that previous section of the splanchnic nerves strongly enhances the levels of plasma TNF-α in conscious rats 90 min after they received intravenous LPS (60 μg/kg). The same reflex mechanism, therefore, applies in conscious as in anesthetized animals. In anesthetized rats, we then determined the longer-term effects of splanchnic nerve section on responses to LPS (60 μg/kg iv). We confirmed that prior splanchnic nerve section enhanced the early (90 min) peak in plasma TNF-α and found that it reduced the 90-min peak of the antiinflammatory cytokine IL-10; both subsequently fell to low levels in all animals. Splanchnic nerve section also enhanced the delayed rise in two key proinflammatory cytokines IL-6 and interferon γ. That enhancement was undiminished after 6 h, when other measured cytokines had subsided. Finally, LPS treatment caused hypotensive shock in rats with cut splanchnic nerves but not in sham-operated animals. These findings demonstrate that reflex activation of the splanchnic anti-inflammatory pathway has a powerful and sustained restraining influence on inflammatory processes. [ABSTRACT FROM AUTHOR]