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BACKGROUND: Chromogranin A (CHGA) is an index granin protein critical for biogenesis and exocytotic release of catecholamine storage granules. It is elevated in plasma of patients with sympathetic over-activity and kidney dysfunction. Several CHGA polymorphisms are associated with hypertensive kidney disease. Previously, we unraveled the molecular mechanism by which CHGA expression is regulated in African Americans carrying a genetic variation associated with hypertensive chronic kidney disease (CKD). METHOD: Experimental CKD mouse model were created by 5/6th nephrectomy (Npx) using wild-type and Chga-/- knockout mouse strains to delineate the role of CHGA in CKD. RESULT: Wild-type-Npx mice expressing Chga developed exacerbated azotemia and fibrosis as compared with their knockout-Npx counterparts. Gene expression profiling revealed downregulation of mitochondrial respiratory complexes genes consistent with maladaptive mitochondria in wild-type-Npx mice, contrasted to knockout-Npx. In healthy individuals, an inverse relationship between circulating CHGA levels and glomerular function was observed. In vitro, mesangial cells treated with CHGA-triggered nitric oxide release by a signaling mechanism involving scavenger receptor SR-A. The CHGA-treated and untreated mesangial cells displayed differential expression of cytokine, chemokine, complement, acute phase inflammatory and apoptotic pathway genes. Thus, build-up of plasma CHGA because of kidney injury served as an insult to the mesangial cells resulting in expression of genes promoting inflammation, fibrosis, and progression of CKD. CONCLUSION: These findings improve understanding of the role of elevated CHGA in the progression of CKD and reveal novel pathways that could be exploited for therapeutic strategies in hypertensive kidney disease.

Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the β-galactosidase binding protein family, during inflammation. Cystinosis is a lysosomal storage disorder and, despite ubiquitous expression of cystinosin, the kidney is the primary organ impacted by the disease. Cystinosin was found to enhance lysosomal localization and degradation of galectin-3. In Ctns-/- mice, a mouse model of cystinosis, galectin-3 is overexpressed in the kidney. The absence of galectin-3 in cystinotic mice ameliorates pathologic renal function and structure and decreases macrophage/monocyte infiltration in the kidney of the Ctns-/-Gal3-/- mice compared to Ctns-/- mice. These data strongly suggest that galectin-3 mediates inflammation involved in kidney disease progression in cystinosis. Furthermore, galectin-3 was found to interact with the pro-inflammatory cytokine Monocyte Chemoattractant Protein-1, which stimulates the recruitment of monocytes/macrophages, and proved to be significantly increased in the serum of Ctns-/- mice and also patients with cystinosis. Thus, our findings highlight a new role for cystinosin and galectin-3 interaction in inflammation and provide an additional mechanistic explanation for the kidney disease of cystinosis. This may lead to the identification of new drug targets to delay cystinosis progression.

Fabric defects in the conventional manufacturing of acoustic panels are detected via manual visual inspections, which are prone to problems due to human errors. Implementing an automated fabric inspection system can improve productivity and increase product quality. In this work, advanced machine learning (ML) techniques for fabric defect detection are reviewed, and two deep learning (DL) models are developed using transfer learning based on pre-trained convolutional neural network (CNN) architectures. The dataset used for this work consists of 1800 images with six different classes, made up of one class of fabric in good condition and five classes of fabric defects. The model design process involves pre-processing of the images, modification of the neural network layers, as well as selection and optimisation of the network's hyperparameters. The average accuracies of the two CNN models developed in this work, which used the GoogLeNet and the ResNet50 architectures, are 89.84% and 95.45%, respectively, showing statistically significant results. The interpretability of the models is discussed using the Grad-CAM technique. Relevant image acquisition hardware requirements are also put forward for integration with the detection software, which can enable successful deployment of the model for the automated fabric inspection. [ABSTRACT FROM AUTHOR]

Demand for second-language (L2) Chinese education for kindergarteners has grown rapidly, but little is known about these kindergarteners' L2 skills, with existing studies focusing on school-age populations and alphabetic languages. Accordingly, we developed a six-subtest Chinese character acquisition assessment to measure L2 kindergarteners' abilities to make associations among the forms, sounds, and meanings of 40 Chinese characters, and administered it to 173 five- and six-year-old L2 kindergarteners in Hong Kong. We found a high model-to-data fit using the two-parameter logistic item response theory model (MS[subscript infit] = 0.87 to 1.07, ps > 0.41). Of the 40 items, 36 exhibited a range of difficulty and good discrimination. Internal consistency reliability and inter-rater reliability were also high. The children scored highest in the category of meaning-sound associations, followed by mapping from meaning to form. The results demonstrate that the instrument is adequately valid and reliable for assessing L2 kindergarteners' character acquisition and imply that child L2 learners may develop abilities to map meanings and sounds prior to their development of form-related mapping. With minor modifications, the developed instrument can be used in various child Chinese L2 programs around the world.

We report the synthesis of alkynylgold(iii) complexes with an electron-transporting phosphine oxide moiety in the tridentate ligand and hole-transporting triarylamine moieties as auxiliary ligands to generate a new class of phosphine oxide-containing bipolar gold(iii) complexes for the first time. Such gold(iii) complexes feature high photoluminescence quantum yields of over 70% in 1,3-bis(N-carbazolyl)benzene thin films with relatively short excited-state lifetimes of less than 3.9 μs at a 20 wt% dopant concentration. Highly efficient solution-processable organic light-emitting devices have been prepared with superior current efficiencies of up to 51.6 cd A-1 and external quantum efficiencies of up to 15.3%. Notably, triplet-triplet annihilation has been significantly reduced, as exemplified by a very small efficiency roll-off of ∼1% at a practical brightness of 500 cd m-2.

The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly. Here, we describe the design of a synthetic human antibody library based on common light chains to generate antibodies with biochemical and biophysical properties that are indistinguishable to traditional therapeutic monoclonal antibodies. We used this library to generate diverse panels of well-behaved, high affinity antibodies toward a variety of epitopes across multiple antigens, including mouse 4-1BB, a therapeutically important T cell costimulatory receptor. Over 200 BsIgG toward 4-1BB were generated using an automated purification method we developed that enables milligram-scale production of BsIgG. This approach allowed us to identify antibodies with a wide range of agonistic activity that are being used to further investigate the therapeutic potential of antibodies targeting one or more epitopes of 4-1BB.

We report the synthesis of alkynylgold(iii) complexes with an electron-transporting phosphine oxide moiety in the tridentate ligand and hole-transporting triarylamine moieties as auxiliary ligands to generate a new class of phosphine oxide-containing bipolar gold(iii) complexes for the first time. Such gold(iii) complexes feature high photoluminescence quantum yields of over 70% in 1,3-bis(N-carbazolyl)benzene thin films with relatively short excited-state lifetimes of less than 3.9 μs at a 20 wt% dopant concentration. Highly efficient solution-processable organic light-emitting devices have been prepared with superior current efficiencies of up to 51.6 cd A-1 and external quantum efficiencies of up to 15.3%. Notably, triplet-triplet annihilation has been significantly reduced, as exemplified by a very small efficiency roll-off of ∼1% at a practical brightness of 500 cd m-2.

The Learning study and the Educational Action Research approaches to educational research are compared, not from a third, neutral point of view, but from the perspective of the former. Hence, the comparison is carried out in terms of how the main point of departure of the Learning study (LS), the question of 'What is to be learned?', is addressed in the two approaches. Both represent critical stances to Educational objectives, the frequently taken-for-granted answer to the question. Educational objectives communicate, however, what the students are expected to become able to do, but not what they need to learn in order to get there. Hence, what is to be learned cannot be stated in advance, prior to the teacher learning what her students need to learn. The two approaches to educational research agree on the principle that what is to be learned has to be found in the interaction between students and teachers; however, there is an important difference between the two concerning the very point of departure. Educational objectives are too wide and imprecise according to LS, the teachers have to find the critical aspects (necessary to appropriate, but not appropriated as yet by the students) of the object of learning. According to Action research, as formulated by Lawrence Stenhouse, educational objectives are too narrow, too limited and limiting. We shall start looking for what is to be learned amongst inherent aspects of the content itself.

Background Study: Previous systematic reviews concluded that online professional‐learning communities (OPLCs) have positive effects on teachers' development, but explored neither the technological affordances that make this possible nor the potential negative impacts of technology use in OPLCs. Objectives: The aim of this study is to systematically analyse previous research on teachers' OPLCs, and thus help answer the question of what technological affordances (dis)empower members of teachers' OPLCs, and how they do so. Methods: This study applied the systematic‐review method. A total of 28 studies were identified and analysed using rigorously defined inclusion and exclusion criteria. The results are reported as a synthesis. Results and Conclusions: First, in theme, the selected articles primarily focused on features of OPLCs and of teachers' knowledge. Second, mixed‐methods approaches were commonly used in the sampled research, and the number of studies employing advanced statistical methods and machine learning increased over time. And third, the reviewed studies' findings suggest that technology supports 'bottom‐up' teachers' communities (as distinct from 'top‐down' professional development organized by educational authorities) in seven ways: that is, by promoting collaboration opportunities, expanding the participants' networks, facilitating knowledge sharing, delivering support more rapidly, providing emotional support, allowing ubiquitous learning, and enabling multiple modes of participation. Lay Description: What is currently known about the subject matter: Previous reviews found OPLCs have positive effects on teachers' development. What their paper adds to this: What technological affordances empower teachers in OPLCs.How technological affordances empower teachers in OPLCs. The implications of study findings for practitioners: The sampled articles primarily focused on OPLC features and teacher knowledge.Mixed‐methods approaches were commonly used.Technology provides various affordances to 'bottom‐up' teachers' communities. [ABSTRACT FROM AUTHOR]