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Collaborative crowdsensing (CCS) requires the recruited team to collaborate closely to complete sensing tasks with high quality of service (QoS). The team recruitment of CCS is mainly influenced by the subjective willingness of participants and the objective trust evaluation of the sensing platform; that is, the higher the subjective mutual willingness to work together and the objective mutual trust among participants, the more efficiency with which the CCS tasks will be achieved. However, the existing research lacks comprehensive consideration of mutual willingness and mutual trust among recruited participants. This results in poor QoS. To address this problem, we propose a novel team recruitment method for CCS that jointly considers the willingness and trust to recruit optimal teams. First, we build a graph convolutional network-based willingness-trust network (GCN-WTN) model for CCS to obtain mutual willingness and trust among participants more accurately. Second, we propose a willingness and trust-based team recruitment (WT-TR) method to recruit the optimal teams for CCS. This method introduces the consensus and similarity constraints into the willingness and trust networks to better meet the collaboration needs of CCS. Finally, we implement a recruitment simulation platform for CCS to simulate the team recruitment process and validate the effectiveness of our proposed method. The experimental results show that the teams recruited by the proposed method can significantly improve QoS for CCS.

Chinese Named Entity Recognition (NER) is an essential task in natural language processing, and its performance directly impacts the downstream tasks. The main challenges in Chinese NER are the high dependence of named entities on context and the lack of word boundary information. Therefore, how to integrate relevant knowledge into the corresponding entity has become the primary task for Chinese NER. Both the lattice LSTM model and the WC-LSTM model did not make excellent use of contextual information. Additionally, the lattice LSTM model had a complex structure and did not exploit the word information well. To address the preceding problems, we propose a Chinese NER method based on the deep neural network with multiple ways of embedding fusion. First, we use a convolutional neural network to combine the contextual information of the input sequence and apply a self-attention mechanism to integrate lexicon knowledge, compensating for the lack of word boundaries. The word feature, context feature, bigram feature, and bigram context feature are obtained for each character. Second, four different features are used to fuse information at the embedding layer. As a result, four different word embeddings are obtained through cascading. Last, the fused feature information is input to the encoding and decoding layer. Experiments on three datasets show that our model can effectively improve the performance of Chinese NER.

Convolution Neural Network (CNN) is an important deep learning method, which is widely used in many fields. However, it is very time consuming to implement CNN where convolution usually takes most of the time. There are many zero values in feature maps and filters, which leads to redundant calculations and memory accesses if dense methods are used to compute convolution. Many works recently make use of sparsity to skip the calculations for zero values to reduce the inference time of CNN. On the GPU platform, current works cannot fully exploit the sparsity of the feature map and achieve satisfactory performance. Therefore, we design a new parallel strategy to transform the feature map into a new storage format to avoid the redundant computation of zero-values on GPUs. Also considering the sparsity in the feature map, we propose a fused storage format to combine the convolution operation with the following pooling operation, in order to further improve the performance. We carry out experiments with mainstream CNN models and achieve better performance compared with cuDNN and cuSPARSE. For VGG-19, ResNet-50, DenseNet-121 and RegNetX-16GF, 1.97 ×, 2.23 ×, 2.74 × and 1.58 × speedups are obtained respectively over cuDNN. The speedups over cuSPARSE are 2.10 ×, 1.83 ×, 2.35 × and 1.35 × respectively when only using the first method.

Serous cystadenoma of the pancreas is a type of pancreatic cystic neoplasm frequently found in clinical practice. Serous cystadenoma of the pancreas can have a varied morphological presentation on imaging examinations. Therefore, it is sometimes very challenging to differentiate serous cystadenoma of the pancreas from pancreatic malignancy. In this study, we present a case of serous cystadenoma of the pancreas showing focally elevated radiotracer uptake on 68 Ga-FAPI PET/CT. Considering potential future clinical use of 68 Ga-FAPI PET/CT in malignancy, awareness of the false-positive findings is important for the differential diagnosis and management of these lesions.

In the context of relatively sufficient research that annotated WNT1 inducible signaling pathway protein 1 (WISP1) as a promoting factor in tumor progression of breast cancer, and identified the effects of ultrasound microbubble technology on enhancing the transfection efficiency and achieving better gene interference, this study managed to investigate the effects of ultrasound microbubble-mediated siWISP1 transfection on proliferation and metastasis of breast cancer cells. To achieve our research objectives, the expression of WISP1 in breast cancer tissues was retrieved from GEPIA website, and the viability of breast cancer cells (SK-BR-3 and MCF7) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for ultrasound intensity screening. After the transfection of siWISP1 by ultrasound microbubble or lipofectamine 6000, the content of WISP1 secreted by cells was detected through Enzyme-linked immunosorbent assay (ELISA), and WISP1 expression in cells was determined by quantitative reverse transcription polymerase-chain reaction (qRT-PCR). Besides, the cell invasion, migration, and proliferation were evaluated by wound healing, transwell, and EdU assays, respectively. In accordance with experimental results, WISP1 was highly expressed in breast cancer tissues, and the 1 W/cm

Reactive oxygen species (ROS) are constantly produced in cells, an excess of which causes oxidative stress. ROS has been linked to regulation of the Hippo pathway; however, the underlying detailed mechanisms remain unclear. Here, we report that MOB1, a substrate of MST1/2 and co-activator of LATS1/2 in the canonical Hippo pathway, interacts with and is acetylated at lysine 11 by acetyltransferase CBP and deacetylated by HDAC6. MOB1-K11 acetylation stabilizes itself by reducing its binding capacity with E3 ligase Praja2 and subsequent ubiquitination. MOB1-K11 acetylation increases its phosphorylation and activates LATS1. Importantly, upstream oxidative stress signals promote MOB1 acetylation by suppressing CBP degradation, independent of MST1/2 kinase activity and HDAC6 deacetylation effect, thereby linking oxidative stress to activation of the Hippo pathway. Functionally, the acetylation-deficient mutant MOB1-K11R promotes lung cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo, compared to the wild-type MOB1. Clinically, acetylated MOB1 corresponds to better prediction of overall survival in patients with non-small cell lung cancer. Therefore, as demonstrated, an oxidative stress-CBP regulatory axis controls MOB1-K11 acetylation and activates LATS1, thereby activating the Hippo pathway and suppressing YAP/TAZ nuclear translocation and tumor progression.

This research aims to explore what challenges the management leaders face when dealing with flexible working employees in a remote working environment, based on the case of one of China's biggest publishing houses—People's Literature Publishing House. Through primary research that targets the managers and employees of the Publishing House, 63 valid questionnaires were collected. The survey was conducted to testify six pairs of variables, specifically the relationship between leaders' communication (independent variable) and employee performance (response variable), between leaders' mental support and employee performance & psychological health, between the use of technology and leadership effectiveness, and between leaders' promotion of flexible organizational culture and employee performance (e.g. engagement, productivity, creativity). The research findings show that leaders' effective communication, mental support, and promotion of flexible organizational culture are great challenges for leaders to manage the employees who work in the virtual environment and improve overall employee performance. The survey results are of great value to the virtual workplace as leaders should emphasize their skills and abilities to deal with flexible working employees, e.g. empowering, effective online communication, and motivating employees in the remote working environment, etc.

This article presents a Lyapunov precise integral-based analysis method for seismic structures with added viscous fluid dampers. This study uses the full stress algorithm as the optimization method, considering the mean square of interstory drifts as the optimization objective, the position of the damper as the optimization object, and the random vibration analysis method as the calculation method to optimize seismic frame structures with viscous dampers. A precise integral solution is derived for the Lyapunov equation based on the general expression of the Lyapunov differential equation for the damping system under the excitation of a nonstationary stochastic process using two types of modulation functions: g(t)=1 and g(t)=t. Finally, the optimal damping arrangement is achieved using this method with a six-layer non-eccentric planar frame. In addition, the optimization results of this study are verified with those in the literature using time-history analysis, which verifies the feasibility and effectiveness of the proposed method. This study provides a method for the optimal configuration of dampers for seismic response of structures, which is beneficial for engineering applications and the protection of seismic structures.

Purpose To evaluate the diagnostic accuracy and clinical impact of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) PET/CT in primary and metastatic breast cancer and compare the results with those of standard-of-care imaging (SCI) and [18F]Fluorodeoxyglucose (FDG) PET/CT. Methods Patients with diagnosed or suspected breast cancer who underwent concomitant [68Ga] Ga-FAPI (FAPI-46) and [18F]FDG PET/CT scans from October 2019 to March 2022 were retrospectively analysed. Breast ultrasound (US) imaging was performed in all treatment-naïve patients as SCI. The maximum standard uptake value (SUVmax), tumour-to-background ratio (TBR), lesion detection rate, and tumour-node-metastasis (TNM) classifications between [68Ga]Ga-FAPI and [18F]FDG PET/CT were evaluated, and compared. Results Twenty-eight women (median age, 52.5 y; range, 28–80 y) were included. Among them, 5 patients underwent evaluation for a definitive diagnosis of suspected breast lesions, 9 underwent initial staging, and 14 were evaluated for the detection of recurrence. The sensitivities of breast US, [18F]FDG, and [68Ga]Ga-FAPI PET/CT for detecting primary breast tumours were 80%, 70%, and 100%, respectively. Regarding the diagnosis of recurrent/metastatic lesions, the per-lesion detection rate of [68Ga]Ga- FAPI PET/CT was significantly higher than that of [18F]FDG, which including local and regional recurrence (128 vs. 88), neck lymph node (LN) metastases (33 vs. 15), abdomen LN metastases (28 vs. 3), bone metastases (146 vs. 59), and liver metastases (28 vs. 11). Compared with [18F]FDG, [68Ga]Ga-FAPI PET/CT upstaged five patients’ TNM staging/re-staging (7/27, 26%) and changed five patients’ clinical management (5/27, 19%). Compared to SCI, [68Ga]Ga-FAPI upstaged ten patients' TNM staging/re-staging (9/27, 33%) and changed the therapeutic regimen of seven patients (7/27, 26%). There was no significant association between FAPI-derived SUVmax and receptor status/histologic type in both primary and metastatic lesions. Conclusion [68Ga]Ga-FAPI PET/CT was superior to [18F]FDG in diagnosing primary and metastatic breast cancer, with higher radiotracer uptake and TBR, especially in the detection of primary/recurrent tumour, abdominal LN metastases, liver, and bone metastases. [68Ga]Ga-FAPI PET/CT is superior to [18F]FDG and SCI in TNM staging and may improve tumour staging, recurrence detection, and implementation of necessary treatment modifications.

Metastases to gastrointestinal tract from breast cancer are very rare and can be diagnostically challenging. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 54-year-old women with such uncommon metastases from breast cancer. Although the primary tumor of breast cancer remained radiologically occult, 68 Ga-FAPI PET/CT showed a far better tumor-to-background ratio than 18 F-FDG PET/CT for detecting the metastatic lesions, especially for detecting the retroperitoneal lymph node and rectal metastases.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and

68 Ga-labeled PET tracer targeting PSMA is a promising diagnostic approach for staging and restating of prostate cancer (PCa), but cases with clinically relevant PCa and false-negative PSMA PET/CT have been reported. In this case, we reported 68 Ga-PSMA, 18 F-FDG, and 68 Ga-FAPI PET/CT findings in a 65-year-old man with de novo metastatic PCa. 68 Ga-FAPI PET/CT detected non-PSMA/FDG-avid primary PCa, consisting with multiparametric MRI findings. The subsequent histopathologic examination confirmed a Gleason 4 + 5 PCa. This case highlighted that 68 Ga-FAPI PET/CT may be a useful imaging modality for primary PCa detection and localization.

Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase activity. However, detailed mechanism underlying LATS1 stability and activation remains elusive. Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4. Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation. Mechanistically, LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation, leading to increased YAP nucleus translocation and promoted target gene expression. Functionally, LATS1-K751Q, the acetylation mimic mutant potentiated lung cancer cell migration, invasion and tumor growth, whereas LATS1-K751R, the acetylation deficient mutant inhibited these functions. Taken together, we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO2) method, thereby avoiding the use of organic solvent. Multiple parameters including theoretical drug loading (DL), presence of pSi, size of scCO2 vessel, PLGA type, and use of co-solvent were investigated with a view to obtaining high DL and a sustained-release for an extended period. The most important finding was that the use of a large scCO2 vessel (60 mL) resulted in a much higher encapsulation efficiency (EE) compared with a small vessel (12 mL). In addition, pre-loading ketamine into pSi slightly improved the level of drug incorporation (i.e. EE and DL). Although the in vitro release was mainly affected by the drug payload, the use of the large scCO2 vessel reduced the burst release and extended the release period for PLGA microparticles with 10% or 20% ketamine loading. Together, our findings provide valuable information for optimization of drug delivery systems prepared with the aid of scCO2.

PET imaging targeting fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of the

Polymorphous adenocarcinoma (PAC) is generally an indolent tumor that mostly commonly affects the minor salivary gland. Polymorphous adenocarcinoma with distant metastases is extremely rare. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT imaging findings in a rare case of epiglottic PAC with multiple bone metastases. 68 Ga-FAPI PET/CT showed superiority over 18 F-FDG PET/CT for detecting the primary and metastatic PAC. This case highlighted that 68 Ga-FAPI may be a promising radiopharmaceutical in the diagnosis of PAC, especially for detecting the PACs arising in uncommon sites.

This paper provides a practical design method for hybrid unbonded post-tensioned precast concrete joints. Such joints featured with self-centering capacities have been widely favored in recent years. However, the absence of design methods hinders their further promotion. To solve the issue, two methods for calculating mechanical behavior of the joints were first studied: characteristic points method and iterative method. The effectiveness of the methods was verified by the existing test results. On this basis, a joint design method considering both yield bearing capacity and energy dissipation capacity was proposed. Moreover, to facilitate design, some factors affecting the bearing capacity were discussed. A five-story frame structure was designed by the proposed design method, and the influence of two design factors on structural response was analyzed by utilizing nonlinear time-history method. The analysis results show that: with the increase of energy dissipation factor αs, the post-earthquake residual deformation of the structure tends to increase linearly, while the accumulated damage of the structure will decrease continuously; both overdesign and underdesign of bearing capacity of the joint are unfavorable; and near-field earthquake may cause irreparable damage to structural columns, making the residual deformation of structures contrary to the self-centering capacity of joints, which shall be considered during engineering design.

This paper investigates one kind of interpolation for scattered data by bi-cubic polynomial natural spline, in which the integral of square of partial derivative of two orders to x and to y for the interpolating function is minimal (with natural boundary conditions). Firstly, bi-cubic polynomial natural spline interpolations with four kinds of boundary conditions are studied. By the spline function methods of Hilbert space, their solutions are constructed as the sum of bi-linear polynomials and piecewise bi-cubic polynomials. Some properties of the solutions are also studied. In fact, bi-cubic natural spline interpolation on a rectangular domain is a generalization of the cubic natural spline interpolation on an interval. Secondly, based on bi-cubic polynomial natural spline interpolations of four kinds of boundary conditions, and using partition of unity technique, a Partition of Unity Interpolation Element Method (PUIEM) for fitting scattered data is proposed. Numerical experiments show that the PUIEM is adaptive and outperforms state-of-the-art competitions, such as the thin plate spline interpolation and the bi-cubic polynomial natural spline interpolations for scattered data.

Clinical concept extraction aims to quickly and effectively extract available data from complex and diverse clinical information, which is a crucial task for medical diagnosis using electronic medical records. Named entity recognition (NER) accurately marks essential information in clinical records based on the characteristics of the target entity, providing a way to extract clinical concepts. In the clinical concept extraction task, the existing methods are not satisfactory to obtain accurate labelling results in the face of large-scale and complex clinical information. To solve this problem, we improve and optimize a named entity recognition method based on the LSTM-CRF model. First, the improved deep neural network model uses two optional configurations of Convolutional Neural Network (CNN) and Bidirectional Long Short-Term Memory (BLSTM) to achieve character-level representation. Then the BLSTM layer obtains the context information of the target word, and the Conditional Random Field (CRF) gives constraints to ensure the standardization of the label. On this basis, Nadam is used to optimize the training process of the network. The experimental results show that our new method has an F1 score of 84.61 on the public dataset of 2010 i2b2/VA concept extraction task, which exceeds the LSTM-CRF model. And the recall of 85.41 is ahead of all the methods evaluated on this data set.

The additional damping ratio (ADR) is an important indicator for evaluating the damping effect of structures with energy-dissipation devices. Most existing methods for determining the ADR require an analysis of the structural dynamic response and complex iterative calculations. An innovative simplified calculation method for determining the ADR of a structure supplemented by nonlinear viscous dampers is proposed. This method does not require the dynamic response of the structure to be calculated and only requires the structural characteristics, excitation frequency, and damper parameters. In this study, several typical calculation methods for the ADR were analysed. Then, a calculation formula for the ADR was derived with consideration of harmonic excitation under the condition where the excitation frequency is equal to the structural natural frequency, without calculation of the structural dynamic response or an iterative process. The effect of the excitation frequency on the calculated value of the ADR with different damping exponents was studied. Accordingly, the response spectrum average period (RSAP) was considered as the excitation period of ground motion to evaluate the excitation frequency, and a simplified calculation method for the ADR considering the effect of the excitation frequency characterised by the RSAP of the ground motion was established. Finally, the accuracy and effectiveness of the proposed method were verified by comparison with ADRs calculated using other methods.

Slug, a member of the Snail family of transcriptional repressors, plays a key role in cancer progression, cellular plasticity, and epithelial to mesenchymal transition (EMT). Slug is a fast-turnover protein and its stability is controlled by post-translational modifications. Here, we identified that Slug is acetylated by acetyltransferase CREB-binding protein (CBP) in breast cancer cells. CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase (HAT) domain, leading to acetylation of Slug at lysines 166 and 211. Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells. Notably, Slug acetylation, mediated by CBP at lysines 166 and 211, doubles its half-life and increases its stability. Further, acetylated Slug downregulates the expression of E-cadherin, the epithelial marker, and upregulates the expression of N-cadherin and vimentin, thereby promoting breast cancer cell migration. In conclusion, the present study demonstrates that CBP-mediated Slug acetylation increases its stability, promoting EMT and migration of breast cancer cells.

The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein-polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of "grafting-to" and "grafting-from" methods. Oligomeric MSEA was synthesized by conventional reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible light-mediated chain extension polymerization of MSEA to obtain a lysozyme-PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability and solubility, and extending their pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Herein, we report a new class of synthetic water-soluble homo-fluoropolymers with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and as such represent a new class of low-fouling polymer for bioconjugation and in vivo tracking.

In this study, we investigated the role of [This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVData were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25-85 years). [The results from this multicenter retrospective analysis justify the clinical use of [• [

Oxidative DNA damage contributes to aging and the pathogenesis of numerous human diseases including cancer. 8-hydroxyguanine (8-oxoG) is the major product of oxidative DNA lesions. Although OGG1-mediated base excision repair is the primary mechanism for 8-oxoG removal, DNA mismatch repair has also been implicated in processing oxidative DNA damage. However, the mechanism of the latter is not fully understood. Here, we treated human cells defective in various 8-oxoG repair factors with H

With the development of learning-based embedding models, embedding vectors are widely used for analyzing and searching unstructured data. As vector collections exceed billion-scale, fully managed and horizontally scalable vector databases are necessary. In the past three years, through interaction with our 1200+ industry users, we have sketched a vision for the features that next-generation vector databases should have, which include long-term evolvability, tunable consistency, good elasticity, and high performance. We present Manu, a cloud native vector database that implements these features. It is difficult to integrate all these features if we follow traditional DBMS design rules. As most vector data applications do not require complex data models and strong data consistency, our design philosophy is to relax the data model and consistency constraints in exchange for the aforementioned features. Specifically, Manu firstly exposes the write-ahead log (WAL) and binlog as backbone services. Secondly, write components are designed as log publishers while all read-only analytic and search components are designed as independent subscribers to the log services. Finally, we utilize multi-version concurrency control (MVCC) and a delta consistency model to simplify the communication and cooperation among the system components. These designs achieve a low coupling among the system components, which is essential for elasticity and evolution. We also extensively optimize Manu for performance and usability with hardware-aware implementations and support for complex search semantics., Comment: 14 pages, 13 figures

The accurate prediction of nonlinear structural behaviors under different seismic intensities is an important basis for seismic resilience assessments of building structures. The moment–rotation relationship is often used to characterize the seismic performance of connections, and is widely used in high-efficiency nonlinear structural analysis. In this paper, a method of calculating the curve using a four-linear equivalent model is presented, aiming to quantify the characteristic point parameters of the moment–rotation curves of monolithic precast beam–column (MPBC) connections for engineering design purposes. The method considered the contribution of the elastic flexure of beams and columns, the relative slip of beam longitudinal bars in the core zone, and the formation of plastic hinges at beam ends to the total deflection. Due to the presence of local complex configurations in MPBC connections, the fine fiber section method was used for moment–curvature analysis of critical beam sections. The determination of the sectional analysis processes was controlled by the strain of steel bars or concrete or their coupling effect. In addition, a two-step method was proposed to construct the moment–rotation relationship of cruciform beam–column connections for solving the deformation compatibility of beams on both sides of the column caused by asymmetric reinforcement and the strength difference between new and old concrete. To reflect the current manufacturing level of MPBC connections, 58 representative specimens reported in recent years were analyzed and classified as type 1–5. All types of MPBC connections and their 18 cast-in situ counterparts were calculated using the proposed method for both verification and quantification. The verification showed that the proposed method had good applicability to both cast-in situ and precast beam–column connections. The quantification showed that the characteristic point parameters were slightly different between these two connections. Accordingly, modification coefficients were suggested for MPBC connections to facilitate design.

Ketamine is used as an analgesic adjuvant in patients with chronic cancer-related pain. However, ketamine's short half-life requires frequent dose administration. Our aim was to develop a sustained release formulation of ketamine with high loading and to evaluate the in vivo pharmacokinetics and biodistribution in mice. Here, ketamine hydrochloride sustained-release lipid particles (KSL) were developed using the thin-film hydration method. The mean (± SD) encapsulation efficiency (EE) and drug loading (DL) of KSL were 65.6 (± 1.7)% and 72.4 (± 0.5)% respectively, and the mean (± SD) size of the lipid particles and the polydispersity index were 738 (± 137) nm and 0.44 (± 0.02) respectively. The release period of KSL in pH 7.4 medium was 100% complete within 8 h in vitro but a sustained-release profile was observed for more than 5 days after intravenous injection in mice. Importantly, the KSL formulation resulted in a 27-fold increase in terminal half-life, a threefold increase in systemic exposure (AUC

Acetate has been shown to have neuroprotective and anti-inflammatory effects. It is oxidized by astrocytes and can thus provide auxiliary energy to the brain in addition to glucose. Therefore, we hypothesized that it may protect against seizures, which is investigated here by feeding glyceryl triacetate (GTA), to provide high amounts of acetate without raising sodium or acid levels.CD1 male mice were fed controlled diets with or without GTA for up to three weeks. Body weights, blood glucose levels, plasma short-chain fatty acid levels, and other hematological parameters were monitored. Seizure thresholds were determined in 6 Hz and maximal electroshock seizure threshold (MEST) tests. Antioxidant capacities were evaluated in the cerebral cortex and plasma using a ferric reducing antioxidant power (FRAP) assay and Trolox equivalent antioxidant capacity assay.Body weight gain was similar with both diets with and without GTA in two experiments. Glyceryl triacetate-fed groups showed 2-3- and 1.6-fold increased acetate and propionate levels in plasma, respectively. Glucose levels were unaltered in blood collected from the tail tip but increased in trunk blood. No differences were found in the activity of cerebral cortex acetyl-CoA synthetase. In the 6 Hz threshold test, seizure thresholds were lower by 3 mA and 2.4 mA after 8 and 14 days, respectively, in the GTA compared to the control diet-fed group, but showed no difference on day 16, showing that GTA has small, but inconsistent proconvulsant effects in this model. In MEST tests, a slightly increased seizure threshold (1 mA) was found on day 19 in the GTA-fed group, but not in another experiment on day 21. There were no differences in antioxidant capacity in plasma or cortex between the two groups.Glyceryl triacetate feeding showed no antioxidant effects nor beneficial changes in acute electrical seizure threshold mouse models, despite its ability to increase plasma acetate levels.

Most of the syntax-based metrics obtain the similarity by comparing the sub-structures extracted from the trees of hypothesis and reference. These sub-structures cannot represent all the information in the trees because their lengths are limited. To sufficiently use the reference syntax information, a new automatic evaluation metric is proposed based on the dependency parsing model. First, a dependency parsing model is trained using the reference dependency tree for each sentence. Then, the hypothesis is parsed by this dependency parsing model and the corresponding hypothesis dependency tree is generated. The quality of hypothesis can be judged by the quality of the hypothesis dependency tree. Unigram F-score is included in the new metric so that lexicon similarity is obtained. According to experimental results, the proposed metric can perform better than METEOR and BLEU on system level and get comparable results with METEOR on sentence level. To further improve the performance, we also propose a combined metric which gets the best performance on the sentence level and on the system level.

Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases.