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Fuzzing is a technique in which anomalous data is fed into software to find potential bugs. It is mainly used to discover vulnerabilities including but not limited to buffer overflows, memory leaks, and crashes when handling abnormal inputs. However, to ensure all inputs are valid in Fuzzing is infeasible in practice due to the high instrumentation overhead. Popular Fuzzers (e.g., AFL) often generate a large number of invalid mutations when performing Fuzzing, which prevents Fuzzers from discovering potential paths that lead to new crashes. More importantly, it prevents Fuzzers from making wise decisions on fuzzing operators. In this article, we propose a mutation sensitive Fuzzing solution Seq2Seq-AFL, in which mutation operator and mutation position are simultaneously taken into account, and different Seq2Seq models are designed to perform optimization scheme. The optimization scheme is capable of efficiently training a function for obtaining mutation operator and mutation position pairs, and utilizes the function to conduct Fuzzing. To verify the effectiveness of our scheme, we construct the dataset with two-dimensional vector data that corresponding to objdump, readelf, and nm programs. The experiment results demonstrate that our proposed scheme significantly improves the performance of the state-of-the-art AFL Fuzzing tool, with the coverage improvements of 13.7%, 17.6% and 6.9% of objdump, readelf and nm, respectively. Especially, Seq2Seq-AFL exposes a total of 21 Crashes for objdump. [ABSTRACT FROM AUTHOR]

Background: Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Methods: Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. Results: FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h−1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. Conclusion: PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. Clinical trial registration: This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142). [ABSTRACT FROM AUTHOR]

To construct an animal model of atrial fibrillation and observe the effect of acute atrial fibrillation on renal water and sodium metabolism in mice. A total of 20 C57 mice were randomly assigned to 2 groups (n = 10/group): control group (CON) and atrial fibrillation group (AF). The mice model of atrial fibrillation was induced by chlorhexidine gluconate (CG) in combination with transesophageal atrial spacing. The urine of the two groups of mice was collected, and then we calculate the urine volume and urine sodium content. The expression of TGF-β and type III collagen in the atrial myocardium of the two groups was detected by immunohistochemistry and Western Blot. The levels of CRP and IL-6 in blood were observed by ELISA, and the NF-κB, TGF-β, collagen type III, AQP2, AQP3, AQP4, ENaC-β, ENaC-γ, SGK1 and NKCC proteins in the kidneys of the two groups of mice was observed by Western Blot. Compared with CON, the expression of TGF-β and type III collagen in the atrial myocardium of the mice in AF were increased, the levels of CRP and IL-6 in the blood in AF were increased, and the renal NF-κB, TGF-β, type III collagen AQP2, AQP3, ENaC-β, ENaC-γ, SGK1 and NKCC protein expression in AF were up-regulated. The level of urine volume and urine sodium content in AF were significantly reduced. In the acute attack of atrial fibrillation, the formation of renal inflammatory response and fibrosis is activated, and the renal water and sodium metabolism is hindered, which is related to the up-regulated of the expressions of renal NKCC, ENaC and AQPs. [ABSTRACT FROM AUTHOR]

Named entity recognition aims to identify entities from unstructured text and is an important subtask for natural language processing and building knowledge graphs. Most of the existing entity recognition methods use conditional random fields as label decoders or use pointer networks for entity recognition. However, when the number of tags is large, the computational cost of method based on conditional random fields is high and the problem of nested entities cannot be solved. The pointer network uses two modules to identify the first and the last of the entities separately, and a single module can only focus on the information of the first or the last of the entities, but cannot pay attention to the global information of the entities. In addition, the neural network model has the problem of local instability. To solve mentioned problems, a named entity recognition model based on global pointer and adversarial training is proposed. To obtain global entity information, global pointer is used to decode entity information, and rotary relative position information is considered in the model designing to improve the model's perception of position; to solve the model's local instability problem, adversarial training is used to improve the robustness and generalization of the model. The experimental results show that the F1 score of the model are improved on several public datasets of OntoNotes5, MSRA, Resume, and Weibo compared with the existing mainstream models. [ABSTRACT FROM AUTHOR]

Postoperative adhesions commonly cause severe complications, and also increase the risk of adhesiolysis. To improve postoperative adhesion, a series of 2-methacryloyloxy ethyl phosphorylcholine conjugated methylcellulose (MC-g-MPC) derivatives were synthesized to utilize the anti-protein adsorption of 2-methacryloyloxy ethyl phosphorylcholine and the thermosensitivity of methylcellulose. The structures of MC-g-MPC derivatives were characterized by Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) analyses, and their thermosensitivities were studied by rheological analysis. The gelling temperature of the MC-g-MPC hydrogel was 33 °C and gelling time of the hydrogel under body temperature was 2.5 min. The morphology of the MC-g-MPC hydrogel was observed by scanning electron microscopy (SEM). The results of in vitro cytotoxicity and immunotoxicity, and hemolysis assays demonstrated the good biocompatibility of MC-g-MPC hydrogels. Following the injection of the MC-g-MPC hydrogel, the postoperative adhesion of damaged ceca in Sprague–Dawley rats was improved when compared with a control group (no treatment). In addition, MC-g-MPC-0.25 hydrogel could downregulate the expression of Col-I and Col-IV collagen proteins, thus exert its anti-protein absorption capacity. Therefore, the MC-g-MPC hydrogel is a promising biomaterial for preventing postoperative adhesion. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) aqueous solution was obtained by the degumming and dissolution of tussah silk, and then the obtained solution was chemically cross-linked with sodium alginate (SA) to form composite membrane, which could be used as a carrier for sustained drug release. The mechanical properties and dissolution rate of such composite membrane together with the drug release behavior under different conditions were investigated. A series of structure-tunable composite membranes were prepared through altering the ingredients proportion, the pH value during fabrication, the concentration of Ca2+, and cross-linking time. The drug release behavior of the corresponding drug-loaded composite membrane was elaborate studied using artemisinin as the model drug. It was found that the drug release rate exhibited a decreasing trend with increasing the SF content, the Ca2+ concentration and the cross-linking time of the corresponding composite membrane. Moreover, the drug release behavior exhibited pH sensitivity, and the drug release rate could be promoted under weak alkaline conditions. [ABSTRACT FROM AUTHOR]

Backgroud:Glioblastoma is a kind of highly malignant and aggressive tumours in the central nervous system. Previously, we found that neurotensin (NTS) and its high-affinity receptor 1 (NTSR1) had essential roles in cell proliferation and invasiveness of glioblastoma. Unexpectedly, cell death also appeared by inhibition of NTSR1 except for cell cycle arrest. However, the mechanisms were remained to be further explored.Methods: Cells treated with SR48692, a selective antagonist of NTSR1, or NTSR1 shRNA were stained with Annexin V-FITC/PI and the apoptosis was assessed by flow cytometry. Cytochrome c release was detected by using immunofluorescence. Mitochondrial membrane potential (MMP, ΔΨm) loss was stained by JC-1 and detected by immunofluorescence or flow cytometry. Apoptosis antibody array and microRNA microarray were performed to seek the potential regulators of NTSR1 inhibition-induced apoptosis. Interaction between let-7a-3p and Bcl-w 3'UTR was evaluated by using luciferase assay.Results: SR48692 induced massive apoptosis, which was related to mitochondrial cytochrome c release and MMP loss. Knockdown of NTSR1 induced slight apoptosis and significant MMP loss. In addition, NTSR1 inhibition sensitised glioblastoma cells to actinomycin D or doxorubicin-induced apoptosis. Consistently, NTSR1 inhibition-induced mitochondrial apoptosis was accompanied by downregulation of Bcl-w and Bcl-2. Restoration of Bcl-w partly rescued NTSR1 deficiency-induced apoptosis. In addition, NTSR1 deficiency promoted higher let-7a-3p expression and inhibition let-7a-3p partly rescued NTSR1 inhibition-induced apoptosis. In addition, let-7a-3p inhibition promoted 3'UTR activities of Bcl-w and the expression of c-Myc and LIN28, which were the upstream of let-7a-3p, decreased after NTSR1 inhibition.Conclusions: NTSR1 had an important role in protecting glioblastoma from intrinsic apoptosis via c-Myc/LIN28/let-7a-3p/Bcl-w axis. [ABSTRACT FROM AUTHOR]

A new side chain liquid crystal aliphatic polycarbonate bearing side-functionalized diosgenyl mesogen, well-defined amphiphilic block copolymer mPEG - b -P(MCC-DHO) was synthesized through the ring-opening polymerization and coupling reaction. The chemical structures and average molecular weights of the monomers and copolymers obtained in this study were characterized using Fourier transform infrared (FT-IR), proton nuclear magnetic resonance (H NMR) spectrum, and gel permeation chromatographic (GPC) measurement. Their mesomorphism was investigated with differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and variable-temperature x-ray diffraction (XRD) measurement. As a result, the monomer DHO and copolymer mPEG - b -P(MCC-DHO) all exhibited fan-shaped texture of a smectic A (SmA) phase on heating and cooling cycles. Furthermore, mPEG - b -P(MCC-DHO) revealed a LC state at body temperature. In addition, XRD suggested that mPEG - b -P(MCC-DHO) showed a SmA phase and exhibited interdigitated packing of side chains. [ABSTRACT FROM AUTHOR]

This paper addresses the issue of designing the detailed architectures of Field-Programmable Gate Arrays (FPGAs), which has a great impact on the overall performances of an FPGA in practice. Firstly, a novel FPGA architecture description model is proposed based on an easy-to-use file format known as YAML. This format permits the description of any detailed architecture of hard blocks and channels. Then a general algorithm of building FPGA resource graph is presented. The proposed model is scalable and capable of dealing with detailed architecture design and can be used in FPGA architecture evaluation system which is developed to enable detailed architecture design. Experimental results show that a maximum of 16.36% reduction in total wirelength and a maximum of 9.34% reduction in router effort can be obtained by making very little changes to detailed architectures, which verifies the necessity and effectiveness of the proposed model. [ABSTRACT FROM AUTHOR]

BSD/I18N project is established for the purpose of internationalizing the 4.3BSD UNIX systems. Its tasks are to provide an internationalized application software development environment, support the 4.3BSD commands/utilities with multi-language processing, and build a complete English and Japanese user environments without excluding other languages like Chinese and Korean. [ABSTRACT FROM AUTHOR]

Several casein hydrogels were synthesized using glutaraldehyde as a crosslinker. The hydrogel prepared from 10 wt% casein and 5 wt% glutaraldehyde at pH = 7.5 showed the best adsorption performance for Cu2+ and methylene blue (MB). The morphology and thermal stability of the hydrogels were characterized by Fourier transform infrared spectrophotometry (FTIR), field emission scanning electron microscopy (FESEM) and thermo gravimetric analysis (TGA). Adsorption data were observed to fit well to pseudo second-order kinetics and the Freundlich-Langmuir switch model. The thermodynamic parameters of the adsorption showed that the adsorption of Cu2+ and MB into casein hydrogel was a spontaneous process. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that remifentanil, an opioid agonist, conferred profound liver protection during hepatic ischemia reperfusion injury (HIRI), in which Toll-like receptors (TLRs) played a crucial role in mediating the inflammatory responses. β-arrestin2, a well-known mu opioid receptor desensitizer, is also a negatively regulator of Toll-like receptor 4 (TLR4)-mediated inflammatory reactions in a mitogen-activated protein kinase (MAPK)-dependent manner. Using the rodent models of hepatic ischemia reperfusion injury both in wild type and TLR4 knockout (TLR4 KO) mice, we found that remifentanil preconditioning could inhibit the expression of TLR4 and reduce the inflammatory response induced by HIRI in wild type but not in TLR4 KO mice. For the in-vitro study, LPS was used to treat RAW264.7 macrophage cells to mimic the inflammatory response induced by HIRI. Remifentanil increased β-arrestin2 expression both in vivo and in vitro, while after silencing β-arrestin2 RNA, the effect of remifentanil in reducing cell death and apoptosis, as well as decreasing phosphorylation of ERK and JNK were abolished in RAW264.7 cells. These data suggested that remifentanil could ameliorate mice HIRI through upregulating β-arrestin2 expression, which may function as a key molecule in bridging opioid receptor and TLR4 pathway. [ABSTRACT FROM AUTHOR]