In vitro/in vivo degradation analysis of trastuzumab by combining specific capture on HER2 mimotope peptide modified material and LC-QTOF-MS.

peer reviewedDegradation analysis of therapeutic mAb is of high interest for critical quality attributes assessment and biotransformation studies. However, some obstacles, including low in vivo concentrations of mAb and complex biological matrices containing IgGs, could seriously interfere with mAb bioanalysis. In this study, a bioanalytical platform was developed for studying in vitro/in vivo modifications of trastuzumab, in which specific capture on mimotope peptide modified material was combined with trypsin digestion and LC-QTOF-MS analysis. It is worth noting that this material exhibits high specificity, suitable dynamic binding capacity, very little non-specific protein adsorption, and thus provides good enrichment and quantification performances for trastuzumab from patient serums. In particular, this bioanalytical platform was successfully applied to the dynamic monitoring of modifications of trastuzumab, such as deamidation, isomerization, oxidation and cyclization. Except for the faster deamidation of LC-Asn-30 and HC-Asn-387/392/393 under serum incubation, similar degradation trends for other sites were observed in phosphate buffer and spiked serum. Differences of peptide modification degrees of trastuzumab in patient serums were also observed. The novel platform exhibited superior specificity than Protein A/G/L based analytical methods, lower cost and higher stability than antigen or anti-idiotypic antibody based analytical methods, ensuring the evaluation of modification sites.Guangzhou Science and Technology Program key project

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses.

Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts

Vibration power flow analysis of laminated composite structures

Laminated composite structures have been increasingly used in engineering structures due to the beneficial properties such as light weight, high stiffness-to-weight ratio, high strength-to-weight ratio and design flexibility. Understanding the vibration behaviour of composite structures is of vital importance to achieve optimal structural design with excellent dynamic performance in terms of low vibration and noise level. However, because of the complexity in modelling and simulation, the vibration energy flow behaviour of laminated composite structure remains largely unexplored and needs detailed investigations. The vibration power flow analysis (PFA) approach is a widely accepted technique to characterize the dynamic behaviour of complex structures. It has been extensively used for vibration analysis of metallic structures, but not of composite materials. This thesis aims to develop effective vibration power flow analysis methods for laminated composite structures to reveal its dynamic behaviour and vibration energy transmission characteristics. PFA based on analytical and numerical finite element methods is carried out to determine the vibration energy input, dissipation, and transmission of composite structures subjected to external excitation force. Both constant stiffness laminated composite (CSLC) plates with straight fibres and variable stiffness laminated composite (VSLC) plates with curvilinear fibres are considered. It is shown that the fibre orientations and stacking sequences have significant effects on the power flow characteristics and dominant vibration transmission paths. For the coupled system such as plates attached with passive devices and coupled L-shaped composite plates, a substructure approach based on analytical and numerical methods is employed to obtain steady-state dynamic response and vibration power flow variables. It is demonstrated that novel inerter-based suppression devices can be attached to the composite plate to modify its vibration transmission and suppress vibration level according to specific design requirements. The fibre orientations of the single or coupled composite plates can be tailored for desirable energy transmission paths. The work described in this thesis reveals that structural design and optimization of composite structures with enhanced vibration suppression performance can be achieved based on vibration energy flow and transmission behaviour. These findings provide new insights for the enhanced dynamic designs of laminated composite plates by tailoring fibre orientations and the suppression of their vibration using inerter-based passive devices. This thesis yields an improved understanding of power flow behaviour of composite structures

Vibration power flow analysis of laminated composite structures

Laminated composite structures have been increasingly used in engineering structures due to the beneficial properties such as light weight, high stiffness-to-weight ratio, high strength-to-weight ratio and design flexibility. Understanding the vibration behaviour of composite structures is of vital importance to achieve optimal structural design with excellent dynamic performance in terms of low vibration and noise level. However, because of the complexity in modelling and simulation, the vibration energy flow behaviour of laminated composite structure remains largely unexplored and needs detailed investigations. The vibration power flow analysis (PFA) approach is a widely accepted technique to characterize the dynamic behaviour of complex structures. It has been extensively used for vibration analysis of metallic structures, but not of composite materials. This thesis aims to develop effective vibration power flow analysis methods for laminated composite structures to reveal its dynamic behaviour and vibration energy transmission characteristics. PFA based on analytical and numerical finite element methods is carried out to determine the vibration energy input, dissipation, and transmission of composite structures subjected to external excitation force. Both constant stiffness laminated composite (CSLC) plates with straight fibres and variable stiffness laminated composite (VSLC) plates with curvilinear fibres are considered. It is shown that the fibre orientations and stacking sequences have significant effects on the power flow characteristics and dominant vibration transmission paths. For the coupled system such as plates attached with passive devices and coupled L-shaped composite plates, a substructure approach based on analytical and numerical methods is employed to obtain steady-state dynamic response and vibration power flow variables. It is demonstrated that novel inerter-based suppression devices can be attached to the composite plate to modify its vibration transmission and suppress vibration level according to specific design requirements. The fibre orientations of the single or coupled composite plates can be tailored for desirable energy transmission paths. The work described in this thesis reveals that structural design and optimization of composite structures with enhanced vibration suppression performance can be achieved based on vibration energy flow and transmission behaviour. These findings provide new insights for the enhanced dynamic designs of laminated composite plates by tailoring fibre orientations and the suppression of their vibration using inerter-based passive devices. This thesis yields an improved understanding of power flow behaviour of composite structures

Vibration transmission and energy flow analysis of L-shaped laminated composite structure based on a substructure method

This study investigates the vibration power flow characteristics of a harmonically excited L-shaped laminated composite structure with flat sub-plates connected at a right angle. A substructure-based power flow analysis (SPFA) method is developed based on analytical, numerical, and hybrid approaches of determining the receptance functions of sub-plates and by using the force balance and geometrical compatibility conditions at the coupling edge. The SPFA methods are then used to evaluate the vibration energy input into the structure and energy transmission through the coupling edge. The power flow density vector is defined, and its time averaged value is used to clearly illustrate the energy sources and sinks as well as the energy transmission paths within the sub-plates. The influence of different combinations of fibre orientations for the sub-plates and the excited dominant global modes of the joined structure on the major vibration energy transfer paths are investigated. It is found that the fibre orientation can have significant effects on transmission paths and potential positions of sinks. From the vibration energy flow perspective, the fibre angles of the integrated laminated composite structure can be tailored for desirable energy transmission paths

Vibration transmission and power flow of laminated composite plates with inerter-based suppression configurations

This paper investigates the vibration transmission and power flow behaviour of harmonically excited laminated composite plates attached with different inerter-based suppression configurations. The substructure approach based on analytical and numerical methods is employed to obtain the steady-state dynamic response. Power flow analysis is carried out to determine the time-averaged power flow input and transmission as well as the kinetic energy of the plate. The power flow density vector is used to show explicitly the vibration transmission paths within the composite plate. It is shown that the fibre orientation and stacking sequences can have significant effects on the time-averaged power flow characteristics as well as the dominant vibration transmission paths. It is also shown that passive spring, damper and inerter elements may be attached to the plate to modify its vibration response and transmission according to specific design requirements. The proposed inerter-based suppression device with two different configurations can reduce the vibration level over a wide frequency range for vibration suppression. The findings may provide insights for the enhanced dynamic designs of laminated composite plates, and the suppression of their vibrations using inerter-based devices

SasWOT: Real-Time Semantic Segmentation Architecture Search WithOut Training

In this paper, we present SasWOT, the first training-free Semantic segmentation Architecture Search (SAS) framework via an auto-discovery proxy. Semantic segmentation is widely used in many real-time applications. For fast inference and memory efficiency, Previous SAS seeks the optimal segmenter by differentiable or RL Search. However, the significant computational costs of these training-based SAS limit their practical usage. To improve the search efficiency, we explore the training-free route but empirically observe that the existing zero-cost proxies designed on the classification task are sub-optimal on the segmentation benchmark. To address this challenge, we develop a customized proxy search framework for SAS tasks to augment its predictive capabilities. Specifically, we design the proxy search space based on the some observations: (1) different inputs of segmenter statistics can be well combined; (2) some basic operators can effectively improve the correlation. Thus, we build computational graphs with multiple statistics as inputs and different advanced basis arithmetic as the primary operations to represent candidate proxies. Then, we employ an evolutionary algorithm to crossover and mutate the superior candidates in the population based on correlation evaluation. Finally, based on the searched proxy, we perform the segmenter search without candidate training. In this way, SasWOT not only enables automated proxy optimization for SAS tasks but also achieves significant search acceleration before the retrain stage. Extensive experiments on Cityscapes and CamVid datasets demonstrate that SasWOT achieves superior trade-off between accuracy and speed over several state-of-the-art techniques. More remarkably, on Cityscapes dataset, SasWOT achieves the performance of 71.3% mIoU with the speed of 162 FPS

Research on Planning Strategy for Urban Community Living Environment for the Elderly That Promotes “Living Mutual Aid”

With the development of urban population aging in China, enhancing the quality of community living environments for the elderly has become crucial. Traditional residential planning focused on functionality, neglecting the elderly’s active participation and mutual aid needs. This paper proposes the development of urban community environments promoting “living mutual aid” to improve elderly life quality and practice active aging. Using qualitative and quantitative methods, the study identifies key components of mutual aid, explores the relationship between mutual aid behaviors and spatial composition, and outlines strategies for designing community environments that support mutual aid. Based on “active aging” theory, the study qualitatively summarizes the concept of mutual aid among the elderly through literature and policy analysis. Surveys, interviews, and observations in Xi’an’s typical communities were conducted, with results analyzed using factor and frequency analysis. The study categorizes mutual aid activities and behavior characteristics, and explores the relationship between behavior and spatial needs using environmental behavior theory. It identifies mutual aid space units and suggests types, paths, strategies, and methods for integrating these units into community environments. The findings provide scientific guidance for urban community planning and valuable references for creating elderly-friendly urban habitats

Slurry Preparation Effects on the Cemented Phosphogypsum Backfill through an Orthogonal Experiment

The cemented phosphogypsum (PG) backfill technique provides a new method for massive consumption of PG, and therefore alleviating the environmental pollution of PG. This study considered the effects of slurry preparation on the performance of cemented PG backfill. A L16(44) orthogonal experiment was designed to analyze four factors, namely the solid content, phosphogypsum-to-binder ratio (PG/B ratio), stirring time and stirring speed, with each factor having four levels. According to the range analysis, the solid content played the dominant role in controlling the bleeding rate, while the setting times strongly depended on the PG/B ratio. In terms of strength development of the backfill, the PG/B ratio was shown to be the most significant factor determining the unconfined compressive strength (UCS), followed by the solid content, stirring time and stirring speed. Furthermore, the results showed that the slurry preparation affected the environmental behavior of impurities that originated in PG. By analyzing the concentrations of impurities in the bleeding water of the slurry as well as the leachates of the tank leaching test, the results showed that the release of F− and SO42− was aggravated clearly with the increase in the PG/B ratio, while the release of PO43− always remained at relatively low levels