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It is of great essence to unveil relationship between structure, mechanical properties, and application of bionic design. Targeting at alleviating the debonding failure issue in the internal structures of the wind turbine blade, the reversed-semi-reentrant (RSRE) honeycomb and the angular gradient (AG) honeycomb with zero Poisson's ratio are considered in the design of the spar/shear web structure. Through finite element methods, the mechanical behaviors of these two types of honeycombs were compared to that of the hexagonal honeycomb. The ability of the RSRE honeycomb to reduce the shear stress on the skin–core interface is proved. The AG honeycomb also proves to have advantages in improving the shear stress distribution inside the honeycomb. Then, the RSRE honeycomb and the AG honeycomb are assembled together to build a complete model of spar/shear web structure. The results of simulations of the whole model under different loading conditions show that these two honeycombs have effectively promoted the mechanical behaviors of the whole model. [ABSTRACT FROM AUTHOR]

• The image generated by MRPM improves the ability of feature representation. • The MDRIRNN fault diagnosis model of the fluid end of the drilling pump is established. • The method realizes the diagnosis of the fluid end under complex working conditions. • The adaptability of the proposed method is verified by MFPT dataset. Accurate fault diagnosis of drilling pump under complex operating conditions poses a significant challenge in drilling operations. This paper addresses the difficulty of extracting fault features from the timing signals of the drilling pump's fluid end under complex working conditions by proposing a method for generating images to represent multidimensional timing signals. Additionally, a multiscale deep recursive inverse residual neural network (MDRIRNN) is introduced to achieve fault diagnosis of the fluid end under such conditions. Firstly, a multidimensional relative position matrix (MRPM) is proposed, which transforms one-dimensional timing signals into three-dimensional images using a 3D data structure. This approach effectively distinguishes the features of different timing signals by adding dimensions. Next, a recursive inverse residual block is designed, and multiscale learning is incorporated to form the MDRIRNN. This model enables the extraction of feature information from the multidimensional images at different scales, thereby enhancing the fault diagnosis process. Subsequently, a fault diagnosis experiment is conducted, demonstrating an average diagnostic accuracy of 96.14 %. Furthermore, the adaptability of the proposed method is validated using the MFPT dataset, achieving a diagnostic accuracy of 99.88 %. This novel method provides a prospecting approach for equipment fault diagnosis under complex operating conditions. [ABSTRACT FROM AUTHOR]

A multifunctional double-network (DN) hydrogel was produced for flexible strain sensor. It was composed of the brittle physical cross-linked network of agar and the ductile chemical cross-linked network of acrylamide (AAm). It had excellent mechanical properties under the interactions of various noncovalent bonds such as electrostatic force, coordination bonds and hydrogen bonds between nano fillers, polyzwitterions and conductive ions. The DN hydrogel had antifreezing performance and adhesion because of the intervention of zwitterionic proline. Prominent strain sensing ability promoted it as a flexible strain sensor for human motion monitoring and motion feedback. In addition, it was also suitable for 3D printing of complex geometry structure. And all these properties were discussed separately. [Display omitted] • A multifunctional double-network (DN) APCP-Ca hydrogel was prepared. • Stretchable, adhesive, antifreezing and 3D printable properties of DN hydrogel were discussed respectively. • DN APCP-Ca hydrogel-based strain sensor and sensing applications were studied. As a new flexible strain sensing material, hydrogels have broad application prospects in the fields of wearable electronic devices, human health monitoring devices and robot aided devices. Therefore, multiple excellent properties of hydrogels were taken into account simultaneously in this work. Double-network (DN) strategy of combining hardness and flexibility was adopted, and the plant materials were adhibited (nanocellulose and proline). The mechanical properties of hydrogels could be significantly improved by combining nanocellulose with conductive ions (stress of 0.293 MPa and strain of 2587%). The excellent antifreezing properties (the conductivity was 0.087 S m−1 at −20 °C) and adhesiveness of hydrogels were endowed with the zwitterionic proline, which was significantly accumulated in plants under low temperature stress. The prepared multifunctional hydrogel was suitable for 3D printing, which provided a new approach for producing complex geometry. Multifunctional hydrogel could be used as a flexible strain sensor to detect human movements, including limb bending, facial expression and vocal vibration because of its outstanding strain sensing characteristics. Hence, we expect it to be an ideal candidate material to flexible electronic detection equipments for human motion detection or machine motion feedback in the future. [ABSTRACT FROM AUTHOR]

Nanocellulose has been adopted to fabricate renewable and thermally stable separators for lithium ion batteries (LIBs). However, the nanofibrils tend to form dense network because of the capillarity during drying, consequently limiting the electrolyte retention capability of the membrane and blocking the migration of ions. To tackle the problems, a novel method is presented to fabricate a nanocellulose based separator with high porosity and multiscale pore structure. The micro-sized pores derived from the dissolution of PS spheres can assure a highly porous feature of the separator. The nano-sized pores fabricated from the ethanol bath further increase the porosity and improve the permeability of the separator. Although the resultant pores weaken the mechanical strength of the separator, the electrochemical performances including the ionic conductivity, interfacial resistance and electrochemical window are ameliorated due to the distinctive microstructures. Moreover, the battery performances, containing capacity retention and rate capability, of the coin battery assembled with the as-constructed separator are proven to be agreeable by the battery test. [Display omitted] • A nanocellulose separator with a multiscale pore structure was prepared. • The ethanol bath was introduced to fabricate nano-sized pores. • The polystyrene spheres were used to produce micro-sized pores. • The as-designed separator could achieve a potential application for LIBs. [ABSTRACT FROM AUTHOR]

[Display omitted] • A cellulose/PEGDA gel polymer electrolyte was prepared via a two-step method. • The interfacial compatibility between GPE and electrodes was greatly improved. • The mechanical robustness and the thermal stability were also enhanced. Cellulose has been adopted to prepare gel poly electrolytes (GPEs) for lithium ion batteries (LIBs). The abundant hydroxyl groups of the cellulose backbones endow GPEs with high ionic conductivities but simultaneously result in poor interfacial resistances. To overcome the above conflict derived from the active hydroxyl groups, a crosslinked cellulose network and a UV-cured PEGDA network are combined to fabricate a double network-based GPE via a green two-step method. On one hand, the as-designed GPE exhibits high electrochemical performances. On the other hand, relying on the strong formation of the hydrogen bonds between the two polymer networks, the interfacial resistance on the GPE-electrode interface turns out to be greatly reduced. Significantly, owing to the enhanced interfacial compatibility, the coin battery assembled with the presented GPE shows favorable cycling performance and rate capability. Moreover, the thermal stability and the mechanical strength of the GPE are improved, indicating a promising practical application for high performance and eco-friendly LIBs. [ABSTRACT FROM AUTHOR]

Recently, hydrogels have attracted considerable interests due to their intrinsic flexibility and adjustable mechanical properties. However, the integration of high conductivity, enhanced mechanical performance, and plasticity into one single hydrogel is still challenging. In this work, TEMPO-oxidized cellulose nanofibers (TOCNF, diameter 20–50 nm, length ≥ 1 um) are used as the efficient dispersant of multiwalled carbon nanotubes (MWCNTs, out diameter 5–15 nm, length 10–30 um). Conductive hydrogels are prepared through a simple one pot process and freeze–thaw cyclic method in combination with Fe3+ ions and TOCNF-MWCNT dispersions in polyvinyl alcohol (PVA) hydrogels. The resulting hydrogels demonstrate high water content (~ 88.8%), mechanical properties (ultimate stress of 1.1 MPa, strain of 336%), and conductivity (0.57 S/m), which can be applied to the preparation of stress or strain sensors. The hydrogel-based resistance sensor is applied to human motion detection, showing a sensitivity of 1.876 kPa−1 with pressure lower than 16 kPa. Similarly, the hydrogel-based capacitive sensor can detect imperceptible pressure of 20 Pa. In addition, the hydrogels also reveal excellent plasticity. In conclusion, the conductive hydrogel possesses excellent comprehensive properties, providing inspiration and potential for the preparation and application of wearable strain sensors. [ABSTRACT FROM AUTHOR]

Gel polymer electrolyte (GPE) is considered as a midway solution of liquid electrolyte and solid polymer electrolyte. Nowadays, the biodegradable and renewable cellulose based GPEs are adopted as promising substitutes for GPEs based on other polymers like PVDF and PMMA. However, the safety concerns derived from the flammability of cellulose still hinders the practical application of the cellulose based GPEs. Simultaneously, the conventional methods to improve the flame-resistance of the host membranes are either unreliable or often invalidate the biodegradability of the GPEs based on cellulose. To achieve the unique combination of biodegradability and high safety, we report the preparation of composite GPEs with flame-retardancy resulted from hydrolysis between phosphorylated nanocellulose (PNC) and hydroxypropyl methylcellulose (HPMC). Besides, the present GPEs are demonstrated to be self-standing and mechanically robust with the advent of PNC. In comparison of the GPEs with various content of PNC, MPC50%/GPC50% are considered as the suitable options thanks to the high tensile strength, satisfactory electrochemical performances and good flame-retardancy. Finally, the LiFePO4/GPC50%/Li coin battery performs a remarkable cycling performance with a high capacity retention of 88.9% at 0.2C and a good rate capability in the battery test. It is anticipated that the as-constructed GPE can contribute to the design on the eco-friendly and high safety batteries in the future. [Display omitted] • A biodegradable gel polymer electrolyte (GPE) based on cellulose composites was prepared. • The phosphorylated nanocellulose (PNC) was prepared and introduced to fabricate the GPE. • The PNC endowed the GPE with enhanced flame-resistance, integrity and mechanical strength. Gel polymer electrolyte (GPE) is considered as a midway solution of liquid electrolyte and solid polymer electrolyte. Nowadays, the biodegradable and renewable cellulose based GPEs are adopted as promising substitutes for GPEs based on other polymers like PVDF and PMMA. However, the safety concerns derived from the flammability of cellulose still hinders the practical application of the cellulose based GPEs. Simultaneously, the conventional methods to improve the flame-resistance of the host membranes are either unreliable or often invalidate the biodegradability of the GPEs based on cellulose. To achieve the unique combination of biodegradability and high safety, we report the preparation of composite GPEs with flame-retardancy resulted from hydrolysis between phosphorylated nanocellulose (PNC) and hydroxypropyl methylcellulose (HPMC). Besides, the present GPEs are demonstrated to be self-standing and mechanically robust with the advent of PNC. In comparison of the GPEs with various content of PNC, MPC50%/GPC50% are considered as the suitable options thanks to the high tensile strength, satisfactory electrochemical performances and good flame-retardancy. Finally, the LiFePO 4 /GPC50%/Li coin battery performs a remarkable cycling performance with a high capacity retention of 88.9% at 0.2C and a good rate capability in the battery test. It is anticipated that the as-constructed GPE can contribute to the design on the eco-friendly and high safety batteries in the future. [ABSTRACT FROM AUTHOR]

Hydrogels have attractive characteristics such as notable biocompatibility, outstanding hydrophilia and efficient mass transport (MT), which makes hydrogel suitable for tissue engineering scaffold materials. Stereolithography is a prevalent method to prepare hydrogel scaffold with complex structure. However, it is difficult to ensure dimension accuracy in printing complex hydrogel scaffold since solvents can migrate in gel and render MT behavior, which consequently induce deformation and dimensional inaccuracy of printed hydrogel. Little investigation of MT of gel in mixture like solution is conducted. Aiming to depict multiple solvents MT in gel, a model is established by mainly modifying the representation of free energy of mixing to the multi-component one. This model is feasible to describe concurrent multiple solvents migration and mechanical deformation for hydrogel in liquid mixtures, which fulfills understanding of multi-component MT. In this work, the transient MT behaviors of poly(ethylene glycol) diacrylate gel in its photocurable solution are investigated by the model. The numerical model is validated by experimental results and then applied to simulate free and confined MT process of the system. It is found that the deformation trend is not monotonous and total gel deformation can be regulated by adjusting printing time. The correspondence between numerical and experimental results proved that this model can promisingly illustrate multi-component MT induced deformation and provide instructions on improving dimensional accuracy for printing hydrogels. [ABSTRACT FROM AUTHOR]

The mask-image-projection-based stereolithography (MIP-SL) is one of the most promising methods for preparing biological scaffolds. In this paper, a mask image planning method based on grayscale regulation is proposed based on the characteristics of the bio-scaffold structure. It is based on support vector machine method and iterative method to intelligently regulate mask pixel gray value, which can achieve low exposure error and accordingly better curing quality. Furthermore, in order to discuss the properties of grayscale regulation, single pixel light intensity function acquisition experiment and stereolithography simulation based on light intensity function and mask grayscale regulation experiment were carried out. Results show that the light intensity distribution function of single pixel follows Gaussian distribution, and the light intensity energy between adjacent pixels will affect each other. The grayscale regulation scheme can improve the degree of reduction of the cured shape of the resin and is beneficial to the curing accuracy. [ABSTRACT FROM AUTHOR]

Gel polymer electrolyte (GPE) comprising the merits of liquid electrolyte (LE) and solid state electrolyte (SSE) has attracted soaring attention. Herein, we develop a GPE with good comprehensive performance by means of mixing the micro carboxylated cellulose fibril (MCCF) and nano carboxylated cellulose fibril (NCCF) in different proportions. In this composite structure, MCCF forms the skeleton of the host membrane of GPE and provides aplenty pores. While NCCF reinforces the connections of the micron cellulose filaments, enhancing the mechanical properties of the membrane. Obtained from the experimental results, the GPE containing 1%wt nano cellulose exhibits a high tensile strength of 40.1 MPa, a good ionic conductivity of 1.84 mS cm−1 at 25 °C and a stable thermal performance up to 220 °C. Simultaneously, the NCM523//Li half cell assembled with this GPE shows a moderate cyclic performance at the ambient temperature of 25 °C. Moreover, such cellulose based GPE is renewable and biodegradable, which can contribute to the environmental protection-oriented development of lithium ion battery industry. Image 1 • The Carboxylated cellulose prepared via TEMPO-oxidization is adopted as host material of GPE for LIB. • The GPE based on the multi-sized carboxylated cellulose possesses satisfactory comprehensive performance. • This work can provide a direction for the development of renewable and biodegradable GPE. [ABSTRACT FROM AUTHOR]

Aiming at the defects of cemented carbide inserts surfaces produced in the conventional grinding process, a cemented carbide inserts chemical mechanical polishing (CMP) process is developed to reduce the insert rake face roughness for the improvement of cutting performance. Especially, an efficient material removal rate (MRR) prediction model for cemented carbide inserts CMP is established considering synthesized effects of multi-factors characteristics such as abrasive particles, the polishing pad, and cemented carbide inserts. Firstly, the contact mechanism between the cemented carbide insert and the polishing pad is analyzed by using the Greenwood and Williamson elastic model. Then the contact model between the abrasive particle and the polishing pad is established based on the Sneddon's hyper-elastic micro-contact mechanics, and the contact model between the abrasive particle and the cemented carbide insert is built by applying the elastic-plastic micro-contact mechanics. Finally, an efficient MRR prediction model is proposed. The experimental results show that when changing the polishing pressure and the polishing disk rotational speed individually, the MRR average error between the predicted value and the experimental value is 1.65% and 2.18%, respectively. This study demonstrates that the proposed model can contribute to CMP preparation of high-performance cemented carbide tools/inserts. • CMP process is adopted to treat the rake face of cemented carbide inserts. • The elastic-plastic deformation of abrasive particles in CMP is analyzed. • The MRR model is established considering the synthesized effects of multi-factors. • The established MRR model may be viewed as an advancement of the Preston model. • The established MRR model is verified by experiment and has high accuracy. [ABSTRACT FROM AUTHOR]

The use of mask-image-projection-based stereolithography process (MIP-SL) in additive manufacturing (AM)for 3D printing of bio-scaffold materials is becoming more widespread. In general, mask optimization, frame compensation, and resin material performance improvement were adopted to improve the curing accuracy of resin in MIP-SL process. In this paper, a mask optimization scheme based on image segmentation technology is developed, where the mask is divided into multiple little squares, hexagons, and triangles. The large-area warping deformation in MIP-SL is therefore transformed to a multiple small area distortion. Digital image correlation (DIC) method is applied to measure the effect of using mask image planning in bio-scaffolds MIP-SL process. A platform of bio-scaffolds resin shrinkage measurement based on DIC method was built to measure the resin deformation under distinct mask image planning. The results show that the deformation of the bio-scaffolds resin during the light-cured process will increase sharply at first and then tend to decrease partially. In addition, shrinkage of square segmentation and hexagon segmentation are reduced by 33% and 27%, respectively. However, the shrinkage of triangle segmentation is hardly reduced because the required time is twice as that of the other two methods. [ABSTRACT FROM AUTHOR]

Remaining Useful Life (RUL) prediction of drilling pumps, pivotal components in fossil energy production, is essential for efficient maintenance and safe operation of such facilities. This paper introduces a deep feature learning method that combines a Convolutional Neural Network (CNN)-Convolutional Block Attention Module (CBAM) and a Transformer network into a parallel channel method to predict the RUL of drilling pumps. Specifically, two parallel channels independently extract time-frequency domain and time-domain features from strain signals and then proceed with degradation estimation through feature learning. The deep features derived independently from the two channels are subsequently amalgamated to predict the RUL of the drilling pump. The proposed method is validated by the operational data from four operating drilling pumps. The comparative analysis confirms the higher accuracy of the proposed method over several existing state-of-the-art approaches. Overall, the proposed method supports the safe and cost-saving-oriented operation and maintenance of drilling pumps. • Time and time-frequency domain features are incorporated as inputs of the model. • Feature weights are adaptively assigned by the CBAM and multi-head attention mechanisms. • A parallel feature extraction structure is created for model generalization and overfitting risk reduction. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia is a leading infectious cause of hospitalization. A few vaccines exist to prevent pneumococcal disease in adults, including a pneumococcal polysaccharide unconjugated vaccine and a protein conjugated polysaccharide vaccine. Previous studies on the human immune response to the unconjugated vaccine showed that the vaccine boosted the existing memory B cells. In the present study, we investigated the human B cell immune response following pneumococcal polysaccharide conjugate vaccination.Methods: Plasmablast B cells from a pneumococcal polysaccharide conjugate vaccinee were isolated and cloned for analysis. In response to primary vaccination, identical sequences from the plasmablast-derived antibodies were identified from multiple B cells, demonstrating evidence of clonal expansion. We evaluated the binding specificity of these human monoclonal antibodies in immunoassays, and tested there in vitro function in a multiplexed opsonophagocytic assay (MOPA). To characterize the plasmablast B cell response to the pneumococcal conjugated vaccine, the germline usage and the variable region somatic hypermutations on these antibodies were analyzed. Furthermore, a serotype 4 polysaccharide-specific antibody was tested in an animal challenge study to explore the in vivo functional activity.Results: The data suggests that the pneumococcal polysaccharide conjugate vaccine boosted memory B cell responses, likely derived from previous pneumococcal exposure. The majority of the plasmablast-derived antibodies contained higher numbers of variable region somatic hypermutations and evidence for selection, as demonstrated by replacement to silent ratio's (R/S) greater than 2.9 in the complementarity-determining regions (CDRs). In addition, we found that VH3/JH4 was the predominant germline sequence used in these polysaccharide-specific B cells. All of the tested antibodies demonstrated narrow polysaccharide specificity in ELISA binding, and demonstrated functional opsonophagocytic killing (OPK) activity in the MOPA assay. The in-vivo animal challenge study showed that the tested serotype 4 polysaccharide-specific antibody demonstrated a potent protective effect when administered prior to bacterial challenge.Conclusions: The findings on the pneumococcal polysaccharide conjugate vaccine responses from a vaccinated subject reported in this study are similar to previously published data on the pneumococcal polysaccharide unconjugated vaccine responses. In both vaccine regimens, the pre-existing human memory B cells were expanded after vaccination with preferential use of the germline VH3/JH4 genes. [ABSTRACT FROM AUTHOR]

Photocurable 3D printing technology has outperformed extrusion-based 3D printing technology in material adaptability, resolution, and printing rate, yet is still limited by the insecure preparation and selection of photoinitiators and thus less reported. In this work, we developed a printable hydrogel that can effectively facilitate various solid or hollow structures and even lattice structures. The chemical and physical dual-crosslinking strategy combined with cellulose nanofibers (CNF) significantly improved the strength and toughness of photocurable 3D printed hydrogels. In this study, the tensile breaking strength, Young's modulus, and toughness of poly(acrylamide- co -acrylic acid) D /cellulose nanofiber (PAM-co-PAA) D /CNF hydrogels were 375 %, 203 % and 544 % higher than those of the traditional single chemical crosslinked (PAM-co-PAA) S hydrogels, respectively. Notably, its outstanding compressive elasticity enabled it to recover under 90 % strain compression (about 4.12 MPa). Resultantly, the proposed hydrogel can be utilized as a flexible strain sensor to monitor the motions of human movements, such as the bending of fingers, wrists, and arms, and even the vibration of a speaking throat. The output of electrical signals can still be collected through strain even under the condition of energy shortage. In addition, photocurable 3D printing technology can provide customized services for hydrogel-based e-skin, such as hydrogel-based bracelets, fingerstall, and finger joint sleeves. [ABSTRACT FROM AUTHOR]

Abstract: Maternal immunity to human cytomegalovirus (HCMV) prior to conception is ∼70% protective against congenital transmission and in utero infection of HCMV. Both functional antibodies capable of neutralizing virus and effective T-cells are believed to be important for the protection. Previous HCMV vaccines have rarely been shown able to induce neutralizing antibody titers comparable to those seen in naturally infected HCMV seropositive subjects. Recent studies link a glycoprotein H (gH) complex to receptor-mediated viral entry of endothelial/epithelial cells and leukocytes. This pentameric gH complex, composed of five proteins (gH, gL, UL128, UL130 and UL131 proteins), is notably missing in all HCMV vaccine previously evaluated in clinic. Here we showed that a HCMV virus, with restored expression of the pentameric gH complex, can induce 10-fold higher neutralizing antibody titers than an attenuated AD169 virus or a recombinant glycoprotein B vaccine in multiple animal species in which viral replication is not expected. Encouragingly, the peak neutralizing titers post vaccination in rabbits and monkeys were within 2–4-fold of the levels determined in HCMV seropositive subjects. Functional antibodies by vaccination could further be improved when formulated with a novel adjuvant, and the titers of the antiviral antibodies were sustained in rabbits for over a year after vaccination. These results indicate that the pentameric gH complex is associated with greatly improved functional antibodies following vaccination, and support a vaccine concept based on a nonreplicating whole HCMV with the pentameric gH-associated epithelial tropism restored. [Copyright &y& Elsevier]

Abstract: Naturally acquired immunity significantly reduces the risk of congenital cytomegalovirus (CMV) infection in future pregnancies. An immune response comparable to that of natural infection has been used as a benchmark for CMV vaccine efficacy; however, the magnitude and persistence of the neutralizing antibody responses in naturally infected women are not completely understood. In this study, we quantitatively analyzed a panel of 375 female CMV convalescent sera ranging in age from 18 to 84 years, for its ability to block virus entry into epithelial cells and fibroblasts, as well as its binding potential to CMV particles. The geometric mean titer of the sera in this panel to neutralize 50% of the virus entry into epithelial cells was 7491, compared to 802 for entry into fibroblasts. The epithelial neutralizing titers were statistically indistinguishable among different age groups, and conformed to a normal distribution. There was a weak correlation between the levels of neutralization and the binding activities to viral particles. Our data confirmed that natural CMV infection in healthy women induces potent neutralizing antibodies against infection of both fibroblasts and epithelial cells. The serum neutralizing activities were maintained at high levels throughout the child bearing age. The corresponding titers may serve as a biomarker for CMV vaccine efficacy. [Copyright &y& Elsevier]

Abstract: Many challenges are encountered in the practical application stage of the impedimetric biosensing technique although an ever-increasing interest has been drawn to this area. Lack of a fast and simple readout method and the corresponding portable, low-cost instrument is one of the greatest obstacles. Here we described a potential attractive solution to this problem, specifically impedance spectra are measured by perturbing the system under investigation with a small-amplitude potential step followed by appropriate processing of the resulting chronoamperometric current response. This measurement strategy makes fabricating a portable impedance measurement instrument for routine analysis with low-cost possible. We constructed such a device which was credit-card sized and mainly comprise a mixed signal microcontroller and several operational amplifiers. The reliabilities of the technique/device were verified by experiments carried out with real electrochemical samples. Relevant problems and limitations of this technique are discussed as well. Obvious advantages with respect to the simplicity, rapidity and ease of miniaturization make the technique/device a competitive candidate for practical point-of-care applications. [Copyright &y& Elsevier]

Abstract: Following the disappointing outcome of the phase IIb test-of-concept step study in which Merck''s adenovirus type 5 (Ad5) HIV-1 clade B gag/pol/nef vaccine failed to demonstrate efficacy in HIV high-risk individuals, an extensive review of the trial and preclinical studies which supported the trial is ongoing. One point of interest is how well preclinical nonhuman primate immunogenicity studies predicted what was observed in humans. Here we compare the HIV-1-specific cellular immune responses elicited in nonhuman primates and human clinical trial subjects to several HIV-1 vaccine candidates. We find that although rhesus macaques are immunologically more responsive to vaccination than humans, the hierarchy in potency of single-modality prime–boost regimens using several vector approaches (adenovirus, DNA, and pox vectors) was well predicted. Vaccine approaches using complex formulations such as novel adjuvants (DNA+CRL1005) or mixed-modality prime–boost (DNA/Ad5; Ad5/ALVAC) did not correlate as well between rhesus macaques and humans. Although the immunogenicity of the vaccines and vaccine regimens evaluated were not all accurately predicted, testing in rhesus macaques generally offers an indispensable tool for ranking the immunological potential of HIV-1 vaccine candidates. [Copyright &y& Elsevier]

Abstract: A novel kind of nanocomposite, titanate nanotubes (TNTs) decorated by electroactive Prussian blue (PB), was fabricated by a simple chemical method. The as-prepared nanocomposite was characterized by XRD, XPS, TEM, FT-IR and Cyclic voltammetry (CV). Experimental results revealed that PB was adsorbed on the surface of TNTs, and the adsorption capacity of TNTs was stronger than that of anatase-type TiO2 powder (TNP). The PB-TNTs nanocomposite was modified onto a glassy carbon electrode and the electrode showed excellent electroactivity. The modified electrode also exhibited outstanding electrocatalytic activity towards the reduction of hydrogen peroxide and can serve as an amperometric sensor for H2O2 detection. The sensor fabricated by casting Nafion (NF) above the PB-TNTs composite film (NF/PB-TNTs/GCE) showed two linear ranges of 2 × 10−5–5 × 10−4 M and 2 × 10−3–7 × 10−3 M, with a detection limit of 1 × 10−6 M. Furthermore, PB-TNTs modified electrode with Nafion (NF/PB-TNTs/GCE) showed wider linear range and better stability compared with PB-TNTs modified electrode without Nafion (PB-TNTs/GCE) and PB modified electrode with Nafion (NF/PB/GCE). [ABSTRACT FROM AUTHOR]

Abstract: We sought to determine how effectively a CD8+ T cell inducing vaccine controls SHIV-89.6P infection in rhesus macaques at a range of challenge times post-vaccination. To this end, twenty eight Mamu-A⁎01 + rhesus macaques were given replication incompetent human serotype 5 adenovirus vector expressing SIVmac239 gag DNA and boosted 24 weeks later. Groups of 4 monkeys were then challenged with SHIV-89.6P at 1, 3, 6, 12, and 24 weeks after the boost. We compared the kinetics of viral load, CD4+ and virus-specific CD8+ T cells in these macaques. Measurements of CD8+ T cells taken before challenge show an exponential decay between 1 and 12 weeks following vaccination (p <0.0001). After week 12, no further decay was observed. Twenty of 24 vaccinated animals maintained more CD4+ T cells and kept their viral load at least one order of magnitude lower than the control animals throughout the chronic phase of the study. All 24 vaccinated animals survived the duration of the study. The viral and T cell kinetics over the first two weeks differed between the vaccinated groups, with more recent vaccination improving the early control of virus (p-value=0.027). The rates of virus specific CD8+ T cell expansion were greater in animals having higher viral loads at one week (r =0.45, p =0.029), suggesting that the kinetics of early viral load may have a role in virus specific CD8+ T cell generation, although these early differences did not lead to different clinical outcomes within the vaccinated animals. [Copyright &y& Elsevier]

Abstract: Safe and efficient methods for in vivo delivery of transgenes of interest must be developed so that the promise of these therapies can be practically used in the clinic. In this work, we describe the use of electrostimulation to enhance the in vivo efficiency of plasmid DNA delivery. The method was optimized to work over a range of moderate frequencies, utilizing low field strengths and simple symmetrical waveforms. After studying several parameters of delivery in mice, we demonstrate how this methodology can be employed to significantly improve both gene expression (over 16-fold) and the immunogenicity of HIV-1 vaccines (over 28-fold) compared to naked DNA in non-human primates. Compared to an efficient viral Ad5 vector system, the gene expression levels of DNA+electrostimulation were surprisingly within a factor of four of the viral delivery system. [Copyright &y& Elsevier]

• An HSV-2 MNA assay correlates with PRNT with and without the addition of complement. • MNA shows greater through-put and 90% reduction in assay time compared to the PRNT. • Human anti-HSV mAbs for virus detection show specificity for HSV gC and gE. • Binding of HSV-1 infected cells to the Fc portion of non-immune human IgG is shown. Plaque Reduction Neutralization Test (PRNT) is the standard assay used for measuring neutralizing antibody responses to Herpes simplex virus type-2 (HSV-2). The PRNT is a cumbersome, time-consuming and laborious assay. The development of a faster, high throughput microneutralization assay (MNA) for HSV-2 viruses carried out in a 96-well format will allow for rapid testing of large numbers of samples for drug and vaccine development. We describe the generation of a MNA that utilizes a pair of anti-HSV human monoclonal antibodies (mAbs) for virus detection in HSV-2 infected Vero cells. Antibodies were generated by B-cell cloning from PBMC's isolated from HSV-1 negative/HSV-2 positive donors. We describe the selection and characterization of the antibodies used for virus detection by ELISA with purified, recombinant anti-HSV glycoproteins, antibody binding in infected cells, and Western Blot. We determine the anti-HSV-2 neutralizing titers of immune sera from mice by MNA and PRNT and compare these results by linear regression analysis. We show that neutralization titers for HSV-2, determined by the 96-well MNA correlate with titers determined by a PRNT completed in 24-well plates in both the absence (R2 = 0.8250) and presence (R2 = 0.7075) of complement. We have successfully developed an MNA that can be used in place of the burdensome PRNT to determine anti-HSV-2 neutralizing activity in serum. This MNA has much greater throughput than the PRNT, allowing many more samples to be processed in a shorter time saving ∼90 % of the time required by the laboratory scientist to complete the task as compared to the traditional PRNT. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries have grown into remarkable energy resource thanks to the superior power and specific energy densities, astounding cycling performance, green sustainability, and extensive applicability. As an important component, the mechanical properties of separator notably affect the assembly quality and working safety of the battery. In this paper, aiming at the electrolyte-immersed and rate-dependent tensile properties of Polypropylene (PP) separators, comprehensive tensile tests concerning different circumstances are conducted. And more significantly, a representative volumetric element (RVE) modelling method is proposed, which is based on image reconstruction technique and realized through inp-launched finite element simulation. The essence of RVE modelling is straightly converting image pixels to finite elements with patterned nodes. The electrolyte immersion effect on PP material is explored through molecular simulation. The experimental results indicate that tensile behaviors are rate dependent and electrolyte immersion would lead to considerable weakening to PP separators. Therefore, mechanical properties of "wet" separators should be seriously considered in future designing. The simulation has successfully calculated the Young's modulus of the PP separators, which inspiringly agrees to that of the experimental. The modelling precision is reliable and the simulating errors are relatively small, revealing worthy applicability and promising outlook of the modelling method. Image 1 • Electrolyte-immersed tensile properties of PP separators are investigated. • Image-based reconstruction modelling method is applied. • Pixels of image are directly transformed into elements for RVE modelling. • Inp file is generated for launching finite element simulation. • The modelling and simulating method shows promising precision applicability. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries have been developing intensively and earn an unprecedented reputation, yet advanced performance and safety issue still require considerable investigation. Separator is vital to comprehensive properties of batteries, where the mechanical properties are key to breaking through of new-type separator. Unfortunately, electrolyte submersion has caused damage to strength of cellulose separator. Whereupon, in this work, cellulose separator is optimized by introducing lignin particles to promote electrolyte-immersed mechanical strength. Experiments are conducted concerning surface morphology, contact angle, porosity, electrolyte uptake, mechanical properties and electrochemical performance. Molecular simulation is implemented to explore the mechanism of tensile behavior of cellulose and lignin subjected to electrolyte solvents. Experimental results confirm positive effect of lignin addition in improving mechanical properties and simultaneously maintaining impressive electrochemical performance of the cellulose/lignin composites separators. Besides, lignin addition amount of 2.5% and 5% is recommended to achieve promising overall properties. Molecular simulation has successfully unveiled that weakening of cellulose separator submerged in electrolyte is resulted by the deformed cellulose amorphous region and the promoting effect of adding lignin is contributed from the new hydrogen bonds generated between cellulose and lignin molecules. Hopefully, this work provides novel insight on preparing remarkable separator and mechanism of materials behavior. Cellulose/lignin composite separator is prepared, whose mechanical properties in electrolyte immersion are improved and validated through experimental and molecular simulating study. Image 1 • Lignin is utilized and verified to improve electrolyte immersed mechanical properties of cellulose separator. • Introduction of lignin causes no harm to electrochemical performance of cellulose/lignin separators. • Addition amount of 2.5% and 5% lignin is suggested for superior comprehensive properties. • Molecular simulation is conducted and successfully unveils mechanism of cellulose and lignin's tensile behavior. [ABSTRACT FROM AUTHOR]

• TEMPO cellulose separators were prepared with different homogenization degree. • Higher homogenization degree contributes to more nano-fibers. • Nano-fibers are good for mechanical but bad for pore and electrochemical properties. • Delicate application of homogenization can lead to better batteries separators. Separator is an essential component for lithium-ion batteries, subtly providing transporting micro-channels for lithium ions and electric insulation between electrodes. In this paper, bleached eucalyptus cellulose pulp is implanted with TEMPO-mediated oxidization and high-pressure homogenization to attain cellulose pulps with both micro- and nano-sized fibers, where the blending ratio is regulated by homogenization times. Then the cellulose pulp is formed into separators through vacuum filtration after uniformly dispersed. Macro-properties, micro-structures, physical properties and electrochemical performance of the cellulosic separators are characterized and analyzed. And t commercial Celgard 2500 polypropylene separator is also investigated as comparison. The influence of homogenizing degree on comprehensive properties of the separators is investigated. Besides, the relationship between micro-structure and electrochemical performance is detailedly discussed. Results show that higher homogenization degree contributes to more nano-sized fibers and less micro-fibers, resulting in smaller porosity, poorer electrolyte uptake and larger contact angle. The nano-sized fibers are effective in promoting mechanical strength of separators, but are negative to the impedance performance. This study has unveiled the impact of high-pressure homogenization on the performance of separators, providing meaningful instruction for further development of qualified cellulose separators. [ABSTRACT FROM AUTHOR]

Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines.

Importance: Human metapneumovirus (hMPV) is a common pathogen causing lower respiratory tract infections worldwide and can develop severe symptoms in high-risk populations such as infants, the elderly, and immunocompromised patients. There are no approved hMPV vaccines or neutralizing antibodies available for therapeutic or prophylactic use. The trimeric hMPV fusion F protein is the major target of neutralizing antibodies in human sera. Understanding the immune recognition of antibodies to hMPV-F antigen will provide critical insights into developing efficacious hMPV monoclonal antibodies and vaccines., Competing Interests: All authors are current or former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock or hold stock options of Merck & Co., Inc., Rahway, NJ, USA. This does not alter the authors' adherence to all journal policies on sharing data and materials.

Pumps are one of the core components of drilling equipment, and their fault diagnosis is of great significance. The data-driven approach has made remarkable achievements in the field of pump fault diagnosis; however, most of them are easily affected by complex background conditions and usually suffer from data scarcity problems in real-industrial scenarios, which limit their application in practical engineering. To overcome the above shortcoming, a novel framework for a model named Hyperparameter Optimization Multiple-Signal Fusion Transfer Convolution Neural Network is proposed in this paper. A convolutional neural network model based on transfer learning is built to promote well-learned knowledge transfer over different background conditions, improve robustness, and generalize the model to cross-domain diagnosis tasks. The multi-signal fusion strategy is involved in capturing system state information for establishing the mapping relationship between the raw signal and fault pattern by integrating the multi-physical signal with the weight allocation protocol. The hyperparameter optimization method is explored in conjunction with the transfer-based model by integrating Grid Search with the Gradient Descent algorithm for further improvement of diagnosis performance. Results show that the proposed model can effectively realize the fault diagnosis of pumps under different background conditions, achieving 95% accuracy.

Tissue engineering (TE) scaffolds with appropriate Poisson's ratio (PR) are suitable for mimicking the environment of native tissues on which cells could survive and thrive better. Herein, cellular structured scaffolds are made by a new composite poly(ethylene glycol) diacrylate/cellulose nanofibril aerogel, with prototypes of the hexagonal, reentrant, and semireentrant models. Scaffolds with different geometry parameters (l, t, α) are designed and simulated by COMSOL to enable precise regulation of their PR. Then, nine groups of scaffolds with different PRs ranging from -0.5 to 0.85 are designed by adjusting geometry parameters and fabricated by using stereolithography and freeze-drying techniques. Subsequently, bone marrow mesenchymal stem cells (BMSc) are cultured on these scaffolds for 21 days, during which CCK8 assay, fluorescence microscope observation, and real-time polymerase chain reaction experiments are performed to characterize the proliferation and differentiation of BMSc. The results reflect that the scaffolds with different PR can provide various stress environments for cells, and the scaffold with zero PR is the most suitable for BMSc differentiating into chondrocytes during early culture experiments. This study suggests that tuning PR precisely is an attractive and effective strategy to provide a cells-suitable environment for scaffold fabrication for TE., (© 2022 Wiley Periodicals LLC.)

Human metapneumovirus (hMPV) belongs to the Pneumoviridae family and is closely related to respiratory syncytial virus (RSV). The surface fusion (F) glycoprotein mediates viral fusion and is the primary target of neutralizing antibodies against hMPV. Here we report 113 hMPV-F specific monoclonal antibodies (mAbs) isolated from memory B cells of human donors. We characterize the antibodies' germline usage, epitopes, neutralization potencies, and binding specificities. We find that unlike RSV-F specific mAbs, antibody responses to hMPV F are less dominant against the apex of the antigen, and the majority of the potent neutralizing mAbs recognize epitopes on the side of hMPV F. Furthermore, neutralizing epitopes that differ from previously defined antigenic sites on RSV F are identified, and multiple binding modes of site V and II mAbs are discovered. Interestingly, mAbs that bind preferentially to the unprocessed prefusion F show poor neutralization potency. These results elucidate the immune recognition of hMPV infection and provide novel insights for future hMPV antibody and vaccine development., (© 2022. Merck & Co., Inc., Kenilworth, NJ, USA and its affiliates.)

Human cytomegalovirus (HCMV) encodes multiple surface glycoprotein complexes to infect a variety of cell types. The HCMV Pentamer, composed of gH, gL, UL128, UL130, and UL131A, enhances entry into epithelial, endothelial, and myeloid cells by interacting with the cell surface receptor neuropilin 2 (NRP2). Despite the critical nature of this interaction, the molecular determinants that govern NRP2 recognition remain unclear. Here, we describe the cryo-EM structure of NRP2 bound to Pentamer. The high-affinity interaction between these proteins is calcium dependent and differs from the canonical carboxyl-terminal arginine (CendR) binding that NRP2 typically uses. We also determine the structures of four neutralizing human antibodies bound to the HCMV Pentamer to define susceptible epitopes. Two of these antibodies compete with NRP2 binding, but the two most potent antibodies recognize a previously unidentified epitope that does not overlap the NRP2-binding site. Collectively, these findings provide a structural basis for HCMV tropism and antibody-mediated neutralization.

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection. It binds to a highly conserved epitope in antigenic site IV of the RSV fusion glycoprotein. RB1 is the parental antibody to MK-1654 which is currently in clinical development for the prevention of RSV infection in infants.

CdS quantum dots with excellent photoelectrical properties embedded in nanocellulose could be exploited for use in photoelectrical ink. In this work, nanocellulose/CdS quantum dot composites were fabricated by controlling the carboxylate content of the nanocellulose and the molar ratio of Cd(2+)/-COOH. New photoelectric inks were prepared based on the composites, in which the CdS quantum dots acted as the pigment and the nanocellulose as the binder. The results of the photocurrent of the composites showed that the photocurrent could be tailored by the carboxylate content and the molar ratio of Cd(2+)/-COOH. And the photocurrent could be as high as 2μA. The surface tension of the photoelectric ink was 27.80±0.03mN/m and its viscosity was 30.3mPas. The photoelectric ink was stable with excellent fluidity and rheology, it could therefore be applied to screen-printing and three-dimensional (3D) printing., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and congenital HCMV infection can lead to birth defects. Developing an effective HCMV vaccine is a high medical priority. One of the challenges to the efforts has been our limited understanding of the viral antigens important for protective antibodies. Receptor-mediated viral entry to endothelial/epithelial cells requires a glycoprotein H (gH) complex comprising five viral proteins (gH, gL, UL128, UL130, and UL131). This gH complex is notably missing from HCMV laboratory strains as well as HCMV vaccines previously evaluated in the clinic. To support a unique vaccine concept based on the pentameric gH complex, we established a panel of 45 monoclonal antibodies (mAbs) from a rabbit immunized with an experimental vaccine virus in which the expression of the pentameric gH complex was restored. Over one-half (25 of 45) of the mAbs have neutralizing activity. Interestingly, affinity for an antibody to bind virions was not correlated with its ability to neutralize the virus. Genetic analysis of the 45 mAbs based on their heavy- and light-chain sequences identified at least 26 B-cell linage groups characterized by distinct binding or neutralizing properties. Moreover, neutralizing antibodies possessed longer complementarity-determining region 3 for both heavy and light chains than those with no neutralizing activity. Importantly, potent neutralizing mAbs reacted to the pentameric gH complex but not to gB. Thus, the pentameric gH complex is the primary target for antiviral antibodies by vaccination.

Neutralizing antibodies are considered an important component of protective immunity against congenital infection of human cytomegalovirus (HCMV), a frequently cited cause of birth defects. An effective HCMV vaccine is desired to induce potent neutralizing antibodies in seronegative females, so that the viral transmission to fetus would be blocked if the women contracted HCMV infections during their pregnancies. We describe a novel microneutralization assay to measure antiviral activities against HCMV in serum samples. The assay is based on detection of a dominant HCMV antigen expressed in cells, using near infrared dye-labeled immune reagents. Since the detection is independent of viral cytopathic effects, this assay format has the appeal of a short turn-around time and a read-out that is not subject to operator experience and judgment, making it a promising platform to support large scale clinical studies. In a serological survey of a cohort of 200 healthy females, we showed that the neutralizing titers measured in this assay are highly comparable to those from a neutralization assay based on an enzyme-linked immunostaining method. Lastly, to demonstrate the utility of this assay to support HCMV vaccine study, we presented the results of neutralizing titers from a rhesus macaque vaccination study., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Simian-human immunodeficiency virus (SHIV) challenge studies in rhesus macaques were conducted to evaluate the efficacy of adenovirus-based vaccines in the context of different major histocompatibility complex class I genetic backgrounds and different vaccine compositions. Mamu-A*01 allele-negative rhesus monkeys were immunized with one of the following vaccine constructs: (i) replication-defective recombinant adenovirus type 5 (Ad5) expressing human immunodeficiency virus type 1 (HIV-1) Tat (Ad5/HIVTat); (ii) Ad5 vector expressing simian immunodeficiency virus (SIV) Gag (Ad5/SIVGag); (iii) Ad5 vector expressing the truncated HIV-1(jrfl) Env, gp140 (Ad5/gp140&#95;jrfl); (iv) Ad5 vector expressing the SHIV-89.6P gp140 (Ad5/gp140&#95;89.6P); or (v) the combination of Ad5/SIVGag and Ad5/gp140&#95;jrfl. Following intravenous challenge with SHIV-89.6P, only those cohorts that received vaccines expressing Gag or Env exhibited an attenuation of the acute viremia and associated CD4-cell lymphopenia. While no prechallenge neutralizing antibody titers were detectable in either Ad5/gp140-vaccinated group, an accelerated neutralizing antibody response was observed in the Ad5/gp140&#95;89.6P-vaccinated group upon viral challenge. The set-point viral loads in the Ad5/SIVGag- and Ad5/gp140&#95;jrfl-vaccinated groups were associated with the overall strength of the induced cellular immune responses. To examine the contribution of Mamu-A*01 allele in vaccine efficacy against SHIV-89.6P challenge, Mamu-A*01-positive monkeys were immunized with Ad5/SIVGag. Vaccine-mediated protection was significantly more pronounced in the Mamu-A*01-positive monkeys than in Mamu-A*01-negative monkeys, suggesting the strong contributions of T-cell epitopes restricted by the Mamu-A*01 molecule. The implications of these results in the development of an HIV-1 vaccine will be discussed.