Final Quality Control Research Articles

Experimental investigation and optimization of the effects of manufacturing parameters on geometric tolerances in additive manufacturing of AlSi10Mg alloy

While the quality of parts produced by additive manufacturing is generally evaluated by surface roughness, relative density, and mechanical properties, the issue of dimensional accuracy is not examined sufficiently. However, dimensional accuracy is very important for the final use and finishing of a product. Since the dimensional change mainly occurs due to shrinkage resulting from the heat energy applied during the sintering process, the effect of production parameters in the additive manufacturing method is quite large. To minimize shrinkage and increase dimensional accuracy, manufacturing parameters need to be optimized and meticulously examined. This study was aimed at determining the effects of manufacturing parameters on geometric tolerances in the production of parts using the additive manufacturing method. AlSi10Mg powder alloy and selective laser melting (SLM) technology were used in the additive manufacturing of this alloy in part production. Twelve different laser powers and scanning speeds, as well as fixed scanning range and layer thickness parameters, were used in production. In determining geometric tolerances, features such as hole diameter change, deviation from angularity, deviation from perpendicularity, deviation from flatness, and deviation from parallelism were taken into consideration. As a result of the study, deviation values increased in high and low laser power/scanning speed combinations. Minimum deviation amounts were obtained in the range of 250–310 laser power and 785–974 scanning speed, which are the middle values of the parameters used. The optimum values of different output responses have been obtained with different production parameters, but for the final use and quality control approval of the product, it is necessary to determine the input parameters at which all output responses are optimal. In this process, the gray relational analysis optimization method, which is one of the multi-criteria decision-making methods, was preferred. As a result of the optimization, the optimum manufacturing parameters for geometric tolerances were determined as the 290/911 laser power/scanning speed combination.

Automatic quality assessment of knee radiographs using knowledge graphs and convolutional neural networks.

X-ray radiography is a widely used imaging technique worldwide, and its image quality directly affects diagnostic accuracy. Therefore, X-ray image quality control (QC) is essential. However, subjectively assessing image quality is inefficient and inconsistent, especially when large amounts of image data are being evaluated. Thus, subjective assessment cannot meet current QC needs. To meet current QC needs and improve the efficiency of image quality assessment, a complete set of quality assessment criteria must be established and implemented using artificial intelligence (AI) technology. Therefore, we proposed a multi-criteria AI system for automatically assessing the image quality of knee radiographs. A knee radiograph QC knowledge graph containing 16 "acquisition technique" labels representing 16 image quality defects and five "clarity" labels representing five grades of clarity were developed. Ten radiographic technologists conducted three rounds of QC based on this graph. The single-person QC results were denoted as QC1 and QC2, and the multi-person QC results were denoted as QC3. Each technologist labeled each image only once. The ResNet model structure was then used to simultaneously perform classification (detection of image quality defects) and regression (output of a clarity score) tasks to construct an image QC system. The QC3 results, comprising 4324 anteroposterior and lateral knee radiographs, were used for model training (70% of the images), validation (10%), and testing (20%). The 865 test set data were used to evaluate the effectiveness of the AI model, and an AI QC result, QC4, was automatically generated by the model after training. Finally, using a double-blind method, the senior QC expert reviewed the final QC results of the test set with reference to the results QC3 and QC4 and used them as a reference standard to evaluate the performance of the model. The precision and mean absolute error (MAE) were used to evaluate the quality of all the labels in relation to the reference standard. For the 16 "acquisition technique" features, QC4 exhibited the highest weighted average precision (98.42%±0.81%), followed by QC3 (91.39%±1.35%), QC2 (87.84%±1.68%), and QC1 (87.35%±1.71%). For the image clarity features, the MAEs between QC1, QC2, QC3, and QC4 and the reference standard were 0.508±0.021, 0.475±0.019, 0.237±0.016, and 0.303±0.018, respectively. The experimental results show that our automated quality assessment system performed well in classifying the acquisition technique used for knee radiographs. The image clarity quality evaluation accuracy of the model must be further improved but is generally close to that of radiographic technologists. Intelligent QC methods using knowledge graphs and convolutional neural networks have the potential for clinical applications.

Twenty questions from the surgeon to the radiologist to better plan an open partial horizontal laryngectomy.

Open partial horizontal laryngectomies (OPHLs) represent a valuable therapeutic option for tumors of the intermediate T-category and, in selected cases, for locally advanced tumors with low-volume extra-laryngeal extension. The eligibility of patients treated with this type of surgery has increased with the introduction of the modular approach to OPHL planning. This strategy follows the introduction of the classification proposed by the European Laryngological Society, based on the extent of horizontal resection. Optimization of the selection is the result of a meticulous work-up process involving close cooperation between experienced surgeons and radiologists, followed by final quality control by pathologists. Computed tomography and magnetic resonance imaging are study methods whose pearls and pitfalls are well known, especially when performed at a high level of expertise. In this paper, based on the experience of two high-volume centers, a checklist of 20 questions addressed by the surgeon to the radiologist before planning an OPHL was proposed. Considerations regarding case selection are reported for each of the questioned parameters. A very simple question-and-answer process is easy to understand and mainly addressed by less experienced colleagues who wish to increase their knowledge and skills in performing this type of surgery.

Grinding burn classification with surface Barkhausen noise measurements

Industrial Barkhausen noise (BN) measurements are commonly utilized for final quality control after machining operations such as grinding to point out grinding burns. Grinding burns might compromise the final use and fatigue lifetime of the ground component. The industrial BN method itself is based on a pre-determined threshold value of the BN rootmean-square value (RMS). Elevated RMS values indicate detrimental changes in the component. Usually, the evaluation of grinding burn severity is not carried out. In this study, real ground cylindrical samples were collected that were rejected based on an industrial quality control with a BN unit. A more detailed BN analysis was carried out for 41 individual grinding burn locations followed by X-ray diffraction based residual stress (RS) surface measurements and residual stress and diffraction peak full-width-at-halfmaximum (FWHM) depth profiles. K-means clustering was applied to profiles to label the data points related to grinding burns of different severity. Three classes of grinding burns were identified and verified by micrographs and hardness. A linear discriminant classification model was then identified between the surface BN measurement features and labeled data points. The classification results were reasonable with about 80 % classification accuracy at worst. They showed that the classes identified can be detected with the surface BN measurements. Thus, the approach presented in this paper shows great potential in the practical use of BN measurement where grinding burns can be detected and evaluated with a surface BN measurement.

Making Anti-CD19 CAR-T Cell Therapy Accessible and Affordable: First-in-Human Phase I Clinical Trial Experience from India

Background: Chimeric Antigen Receptor (CAR) T cells therapy has shown remarkable success in haematological malignancies. However, complexity of the manufacturing platform and exorbitant costs of the available therapy limits their accessibility in limited resource settings including India. Recently, we developed a novel humanized anti-CD19 CAR-T cell therapy (HCAR19) and showed its efficacy in preclinical models (Dwivedi et al, Mol Cancer Ther. 2021). Here we report our experience of HCAR19 manufacturing in an integrated platform for first-in-human Phase-I clinical trial. Further, we performed the cost analysis of CAR-T delivery from development to clinic. Methods: Lymphocytes were collected from 17 patients of r/r B cell malignancies (DLBCL, transformed follicular lymphoma, PMBCL and B-ALL) through apheresis (Fresenius Fomtek or Spectra Optia) upon receiving the regulatory approvals from central and local agencies. CD3+ T cells were enriched and activated using CTS™Dynabeads™ CD3/CD28 for 36-48 hours followed by consecutive double transduction with CD19 encoding lentivirus vector. Final product was harvested, cryopreserved and stored in ultra-low temperature until further use. All steps were carried out in closed gas permeable bags. Final product quality control (QC) assays were performed by flowcytometry, ELISA, analytical and cell-based assays. The cost of CAR T cell manufacturing was calculated for unit economics on fully scale production model by standard costing methodology. The final unit economics included cost of goods and services (COGS), overhead costs, financing costs of infrastructure, R&D and clinical trials costs. The model was scaled towards a 200 patient per annum in a centralized manufacturing facility. Results: Of the 19 patients enrolled in the study, only 17 patients underwent apheresis procedure for harvest of total 5-10 X 109 mononuclear cells. HCAR19 cells from all 17 patients were manufactured successfully in functionally closed integrated manufacturing platform. The required HCAR19 dose was achieved within 8 days of culture (dosage range: 1.78 x 106 - 17 x 106 viable HCAR19/kg). The transduction efficiency of HCAR19 in r/r DLBCL, r/r PMBCL and r/r B-ALL was 37.7 ± 6.64%, 28.8 ± 8.81% and 34.6 ± 9.72% (Mean ± SEM) respectively . The HCAR19 showed a robust expansion (~20-fold) ex vivo and maintained the presence of potent anti-tumor subsets like naïve and central memory T cells (Figure 1a). Final product from all 17 patients qualified the QC release criteria for safety, identity, purity and potency as per specifications. Finally, the unit economics in fully-scaled production model indicated the estimated cost of CAR-T cell delivery was approximately 30,000 USD (or 25,00,000 INR) per dosage including logistics, lentiviral vector cost and quality control (Figure 1b). The major costs incurred were towards consumables, overhead and financing costs of clinical trials and infrastructure. There was very minor components of logistics and utility costs. More importantly, the major contributors of overall low cost of CAR-T delivery in our settings were frugal R&D costs in an academic setting, scalable integrated manufacturing platform, and highly qualified yet economical manpower. Conclusions: We developed a robust, scalable and highly affordable CAR-T cell therapy platform (product and process development, and first-in-human clinical study), and proven its clinical delivery successfully with our first indigenous HCAR19 product. Given the benefit of affordable platform to broader socio-economic base of patients, the cell and gene therapy will be poised for a transformational change as a mass therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Generalized Strategy From S‐Wave Receiver Functions Reveals Distinct Lateral Variations of Lithospheric Thickness in Southeastern Tibet

AbstractThe selected rotation angle and deconvolution time window during S‐wave receiver function (SRF) calculations, and the final SRF quality control may introduce artificial interference. Here we overcome these problems by proposing a new strategy named GC_SRF for obtaining the lithospheric thickness from S‐wave receiver functions, which employs grid search and correlation analysis to obtain reliable SRFs. Extensive tests using synthetic and real data suggest that the GC_SRF strategy is a robust and reproducible approach for estimating lithospheric thickness. Specifically, this GC_SRF strategy can restore the weak Sp phases from full wavefield synthetic seismograms. Clear and distinct discontinuity patterns that do not involve artificial interference compared with those obtained in previous studies of southeastern Tibet are produced here. The post‐stack migrated SRFs reveal distinct lateral variations of lithospheric thickness in southeastern Tibet: (a) Tengchong volcano has a thin crust and thin lithosphere–asthenosphere boundary (LAB) (∼90 km); (b) the Chuandian region has a thicker crust and either a poorly defined or unclear LAB. The absence of a continuous LAB in the Chuandian region may suggest lithospheric regrowth due to the recovery processes of the mantle plume; (c) a thinner crust and clear LAB of ∼160 km depth is presented beneath the Sichuan Basin.

Motion feature based melt pool monitoring for selective laser melting process

Since various build defects in the Selective laser melting (SLM) process are found to be associated with the instability of melt pool, the melt pool monitoring is particularly important for the final product quality control. Previous studies focus on the geometric features to describe the changes of the size and shape of melt pool, which are not sufficient to characterize the dynamic variations of the melt pool during the build process monitoring. To solve this problem, a new motion feature is introduced to describe the moving melt pool. The melt pool and spatters are extracted by thresholds combined with the connected component analysis method. The distance between the centroid and the boundary of melt pool is calculated from the unfolded clockwise at a step angle, which constructs a high dimensional feature vector as the motion features. The k-means clustering algorithm is applied to cluster the motion features under varied process parameters, aiming at construct the link between the melt pool states and processing parameter for the quality control. The research results have shown that the extracted motion features can describe the variation of melt pool more accurately than the traditional geometric features, and they can distinguish the moving direction and melted states of over melting, partial melting and defects simultaneously. This research provides a new approach for intelligent online monitoring of the SLM process.

Genome-wide association study (GWAS) of growth traits in olive flounder (Paralichthys olivaceus)

Traits linked to growth performance in farmed fish are major drivers of profitability in aquaculture systems. Given the importance of growth-related traits, there have been efforts to unravel the genomic architecture of growth traits and to identify key genes or genomic regions useful as selection markers in various species. Such markers would increase the accuracy of selection and improve rates of genetic progress for growth improvement in breeding programs. Olive flounder (Paralichthys olivaceus) has a considerable market value in Asia and is mainly cultured in South Korea. To facilitate a breeding program for this species, a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms (SNP) associated with growth traits. In total, 1800 fish were measured for body weight (BW), total length (TL), and maximum body depth (BD). Fish were genotyped using the Affymetrix® Axiom® myDesign™ Genotyping Arrays; 1009 fish and 58,756 SNPs remained after the final quality control check. According to the phenotypes, female fish recorded higher BW, TL, and BD than male counterparts of the same age, revealing a sex-dependent growth pattern. There was a strong positive phenotypic correlation (0.945–0.965) and a moderate genotypic correlation (0.286–0.332) between the three growth performance traits of the 1009 fish. Eight SNPs were identified above the significant (p < 8.5 × 10−7) and suggestive (p < 1 × 10−5) thresholds for all traits, and they were mapped primarily onto chromosomes 23 and 24. According to the GWAS analysis, genotypes at loci AX-419206420 and AX-419307742 significantly affected the growth performance of the population. Gene ontology (GO) analysis was performed on 30 candidate genes with notable growth performance effects (p < 1 × 10−4) and GO terms related to neuron development, molecule binding and cytoskeleton organization were highly enriched. Our findings may contribute to understanding of the molecular basis of growth regulation and promote the use of SNP-based genomic selection in flounder culture.

Monitoring the structural condition of parts of K 250 centrifugal compressors at different stages of production

Among the existing methods of ensuring the production of goods, an important place is occupied by the input and final quality control of metal products in production. The main task of the input control is to constantly ensure the necessary level of quality, fixed in regulatory documents, by directly checking each batch of supplied metal. The use of active quality control directly during the production of goods allows to prevent and detect defects at the initial stages and during the manufacture of finished types of metal products. Control at the output of the production system has the main purpose to prevent the transfer of defective products to the consumer or to the subsequent technological phases (stages). Goal. The goals is development of methods for monitoring the parts of K-250 centrifugal compressors at various stages of production and selection of the optimal mode of heat treatment of rotor elements made of structural steel of the martensitic class of the 34KHN1MA brand. Method. The control included mechanical tests, metallographic studies of blanks and finished parts, as well as non-destructive testing for internal defects and surface quality. Results. A comprehensive input control of the macro- and microstructure, as well as the mechanical properties of blanks made of 34KHN1MA steel was carried out. A mode of improving the properties of critical parts of a centrifugal compressor made of 34KHN1MA steel by heat treatment is proposed. Control of the finished product was carried out, including mechanical tests, microstructure studies, as well as non-destructive surface quality control.

(Invited) A Functional Analysis of MEA Attributes and Properties for the Quality Control of Polymer Electrolyte Fuel Cells

Quality control (QC) is essential for the industrialization of the polymer electrolyte fuel cell (PEFC) technology, which assures the reliability of the components/sub-components, offers specification guidance for new entrants in the supply chain, and helps to reduce cost of the final product. With respect to the standardization of component/sub-component specifications, it is of great importance to identify key attributes and characterize the properties of key component and its sub-components. As the PEFC technology is being commercialized and research activities around PEFCs are being reoriented towards manufacturing issues, there is an urgent need for the QC of the key component, membrane electrode assembly (MEA), of PEFCs. As a matter of fact, the lack of standard methods, protocols and tools for the incoming, in-process and final QC of the MEA, especially, the lack of in-line, non-destructive and roll-to-roll tools for the QC of the MEA, has become one of key barriers for the PEFC commercialization.In this context, the objective of this work is to conduct a functional analysis of attributes and properties for the sub-components of the MEA, including membrane, gas diffusion layer (GDL), catalyst layer (CL), and catalyst coated membrane (CCM). To address the full spectrum of the MEA sub-components, ink is also included. The main functions of the MEA sub-components are given in Figure 1, where MPL represents the micro-porous layer of the GDL and PEM represents the proton exchange membrane or polymer electrolyte. As the attributes and properties of each MEA sub-components strongly correlate with the cell performance and longevity, this work will facilitate the investigation, diagnosis and characterization of each sub-components for the purpose of QC. This functional analysis is performed by breaking down the main functions for each sub-component of the MEA, categorizing the supporting attributes and related properties under respective functions, identifying measurement methods existing or under-development for each property and prioritizing each property for the QC of the MEA. This functional analysis links functions to attributes, properties, and measurements, with a final presentation in the format of a table with columns designated for function, attribute, property, measurement, and priority for QC.This work is accomplished through a close collaboration within a global fuel cell network, including fuel cell auto makers, fuel cell manufacturers, component suppliers, and research organizations. We believe that this work is of great importance to describe specifications and develop standards and codes for the sub-components of the key PEFC component, MEA. It is also important to identify the properties that are critical to QC. In addition, this work helps to address the discrepancy in the understanding the terms for QC along the supply chain and harmonize the language of QC. It also provides a basis for the development of QC tools for the MEA.Figure 1 Schematic of the MEA and the main functions of the MEA sub-components Figure 1

NES-DMA with Charge-reduction based on Soft X-ray Radiation: Analysis of a Recombinant Monoclonal Antibody

Due to the fast growing importance of monoclonal antibodies in biomedical research, bioanalytics and human therapy, sensitive, fast and reliable methods are needed to monitor their production, target their characteristics, and for their final quality control. Application of a nano electrospray (nES) with soft X-ray radiation (SXR) based charge reduction and differential mobility analysis (DMA, aka nano electrospray gas-phase electrophoretic mobility molecular analysis, nES GEMMA) allows the size-separation and detection of macromolecules and (bio-)nanoparticles from a few nm up to several hundreds of nm in diameter in a native-like environment. The current study focuses on the analysis of a 148 kDa recombinant monoclonal antibody (rmAb) with the above mentioned instrumental setup and applying an universal detector, i.e. a water-based condensation particle detector (CPC). Next to the intact rmAb, its aggregates and fragment products after digestion with IdeS protease were analyzed. Additionally, influence of temperature treatment and pH variation on the stability of the rmAb was monitored. In this context, changes in electrophoretic mobility diameter (EMD) values, peak shape, and signal intensity based on particle numbers were of interest. Molecular weights calculated by application of a correlation derived from respective standard protein compounds were compared to mass spectrometric values and were found to be in good accordance. To conclude, we demonstrate that nES-DMA is a valuable tool in the characterization and quality control of rmABs.

Development and validation of a simple and reliable alternative method for process monitoring and final product quality control during fatty acid ethyl esters production

As the production of biofuels increase, there is an urgent need to easily analytically control their production at the plant level as well as to assess the quality of the final products. Especially method capable of determining fatty acid ethyl ester content of 96.5% is crucial for utilization in praxis. In this work, a refractive index method with required sensitivity was developed and validated by means of a standard reference gas chromatography method. Validation with a considerable set of real unique samples obtained at pilot scale was performed for both purposes – process monitoring at high conversions and final product quality control. The results confirmed a favourable degree of accuracy with a relative deviation lower than 3.5% from the reference value given by the gas chromatography. Moreover, application of the method for quality control of fresh and long-term stored samples revealed that the deterioration of final products during storage can be detected. The developed refractive index method is thus suitable for the simple and rapid evaluation of the quality of produced fatty acid ethyl esters and for analytical monitoring of their production process.

Technical analysis of full-scale Construction and Demolition Waste treatment plants: case studies of the Lombardy Region, Italy

Construction and demolition activities in Italy and the Lombardy Region produce a considerable amount of wastes that can be valorised as secondary raw materials. The recovery of construction and demolition wastes is severely limited by the lack of consolidated and sustainable treatment chains and by the strong variability of their environmental characteristics that may generate potentially dangerous effects for the environment. The purpose of this study was to evaluate and technically define the current treatment chains in the Province of Brescia (Lombardy) by analyzing three full-scale treatment plants in order to highlight barriers to demolition waste recovery and propose possible solutions and improvement strategies. To best represent the entire management and treatment system, the analysis was developed on all the acceptance, treatment, and final quality control phases. Moreover, chemical composition and leaching data on demolition wastes and recycled aggregates were collected from the three treatment plants and statistically analyzed to assess their potential recovery according to the Italian legislation. Mixed non-hazardous waste is the fraction mostly managed by recycling plants and mixed recycled aggregates are the main products obtained from the treatment. These are mostly used in roads and in geotechnical applications. Chemical composition results showed that the pH is generally alkaline and tin and benzene are the most critical elements for both demolition wastes and recycled aggregates with respect to the regulatory limit values. Total chromium was identified as a critical compound in leachates. The results of the statistical analysis confirmed that chromium was mainly released by cement materials.

Designing a Quality System using the Goals Programming Method -An Applied Research

Due to the continuous development in society and the multiplicity of customers' desires and their keeping pace with this development and their search for the quality and durability of the commodity that provides them with the best performance and that meets their needs and desires, all this has led to the consideration of quality as one of the competitive advantages that many industrial companies compete for and which are of interest to customers and are looking for. The research problem showed that the Diyala State Company for Electrical Industries relies on some simple methods and personal experience to monitor the quality of products and does not adopt scientific methods and modern programs. The aim of this research is to design a system to monitor the production quality of the transformer (400/11 KVA) through the use of a method that helps to make decisions of a quantitative multi-objective nature, which is the method of lexicographic goal programming that the researcher used to integrate the preferences of the decision-maker in monitoring the quality of the production of the transformer (400/11 KVA). Using the two programs (Excel and Lingo) in constructing and solving the mathematical model that was applied in the sections (outer and inner iron core, winding and isolating, final assembly and quality control). The results obtained were efficient, as they achieved the least possible deviations from all the target values ​​for all goals

Assessment of process stability and capability in a manufacturing organization: a case study

Quality is considered asthe principal factor that determines the long-termsuccess or failure of any organization. Organizations perform quality control by monitoring process output using Statistical Quality Control, performed as part of the production process (Statistical Process Control, SPC) or as a final quality control check (Acceptance Sampling).SPC is a major quality management statistical tool and its instruments (control charts and capability analysis) are applied to virtually any type of organization (manufacturing, services or transactions - for example, those involving data, communications, software, or movement of materials). The aim of this paper is to present a case study, realized in a manufacturing organizationfrom Sibiu, for a new product used in the automotive industry to check its conformance to designed requirements. The output data were analyzed using statistical analysis software Minitab.

Automated total kidney volume measurements in pre-clinical magnetic resonance imaging for resourcing imaging data, annotations, and source code

The objective of this study was to validate a fully automated total kidney volume measurement method for pre-clinical rodent trials that is fast, accurate, reproducible, and to provide these resources to the research community. Rodent studies that involve imaging are crucial for monitoring treatment efficacy in diseases such as polycystic kidney disease. Previous studies utilize manual or semi-automated segmentations, which are time consuming and potentially biased. To develop our automated system, a total of 150 axial magnetic resonance images (MRI) from a variety of mouse models were manually segmented and used to train/validate an automated algorithm. To test the longitudinal application of the model, four mutant and four wild-type mice were imaged sequentially over three to twelve weeks via MRI. Segmentations of the kidneys (excluding the renal pelvis) were generated by the automated method and two different readers, with one reader repeating the measurements. Similarity metrics and longitudinal analysis were calculated to assess the performance of the automated compared to the manual methods. The automated approach required no user input, besides a final visual quality control step. Similarity metrics of the automated method versus the manual segmentations were on par with inter- and intra-reader comparisons. Thus, our fully automated approach described here can be safely used in longitudinal, pre-clinical trials that involve the segmentation of rodent kidneys in T2-weighted MRIs.

Quality evaluation of three brands of type 1 wheat flour commercialized in Belém, Pará, Brazil

Wheat is a crop rich in nutrients. In Brazil, about 130,000 properties produce the cereal, involving 800,000 people. Due to its rheological properties, that is, the extensibility capacity of this cereal stands out in the manufacture of breads, in addition to the increasing use of flour in the food industry. Thus, the use of some physical-chemical analysis to determine the quality of wheat flour according to the normative instruction from Agriculture, Livestock and Storage Ministry (MAPA) document nº 8/2005. Wheat flour samples of type 1 (A, B and C) were acquired in a supermarket located in the city of Belém / PA, posteriorly sent to the Centro de Tecnologia Agropecuária - CTA at the Universidade Federal Rural da Amazônia (UFRA), to determine granulometry, grease acid, protein, humidity and ashes. Regarding to granulometry analysis, samples A and C were above the tolerance values proposed by the Ministry of Agriculture and Livestock - MAPA. Grease acid and humidity were inside to MAPA tolerance standards for all samples. In ashes determining, the values showed that all three samples were out of the quality standard, in addition, about protein content, the samples were also characterized as out of type. Therefore, there is a need for better inspection by the responsible authorities, since cultivation conditions until the final quality control of the product.

Obtaining High-Quality Transcriptome Data from Cereal Seeds by a Modified Method for Gene Expression Profiling.

The characterization of gene expression is dependent on RNA quality. In germinating, developing and mature cereal seeds, the extraction of high-quality RNA is often hindered by high starch and sugar content. These compounds can reduce both the yield and the quality of the extracted total RNA. The deterioration in quantity and quality of total RNA can subsequently have a significant impact on the downstream transcriptomic analyses, which may not accurately reflect the spatial and/or temporal variation in the gene expression profile of the samples being tested. In this protocol, we describe an optimized method for extraction of total RNA with sufficient quantity and quality to be used for whole transcriptome analysis of cereal grains. The described method is suitable for several downstream applications used for transcriptomic profiling of developing, germinating, and mature cereal seeds. The method of transcriptome profiling using a microarray platform is shown. This method is specifically designed for gene expression profiling of cereals with described genome sequences. The detailed procedure from microarray handling to final quality control is described. This includes cDNA synthesis, cRNA labelling, microarray hybridization, slide scanning, feature extraction, and data quality validation. The data generated by this method can be used to characterize the transcriptome of cereals during germination, in various stages of grain development, or at different biotic or abiotic stress conditions. The results presented here exemplify high-quality transcriptome data amenable for downstream bioinformatics analyses, such as the determination of differentially expressed genes (DEGs), characterisation of gene regulatory networks, and conducting transcriptome-wide association study (TWAS).

Methodology for Preparation of Audit Entities to External Control of the Quality of Audit Services

The requirements to the system of control over the quality of audit services are analyzed, which are specified in the Law of Ukraine “Audit of Financial Statements and Auditing” from 21.12.2017 No 2258-VIII; Directive of the Ministry of Finance of Ukraine “Approval of the Procedure for Inspection of the Quality Control of Audit Services” from 29.08.2019 No 362; Resolution of the Council for Supervision over Auditing at the State Institution “The Body of Public Supervision over Auditing” from 30.08.2019 No 6/7/13 “Information Questionnaire of Auditing Entity”. It is demonstrated that the quality control system requires corrections of the following: responsibilities of administration and staff of auditing entities for use of the adopted intra-firm provisions on the quality control system, requirements of ISQC1, IAS, the Law of Ukraine “Audit of Financial Statements and Auditing”; the requirements to staff (quality controller, reviewer, assignment partner); identification of threats to the independence and the auditor’s response on the assessed threats; the requirements to reviews of complaints, complicated issues; issues related with non-stop professional training of auditors. Special attention of auditors need to be drawn to the fact that the policies and procedures of the quality control system do not have to be confined to the audit of financial statements, but have to apply to other assignments on giving confidence and related auditor services. Besides that, assessment of threats to the independence has to be conducted for non-auditor services specified in Article 6 of the aforementioned Law of Ukraine.&#x0D; The studies conducted by the author allowed to elaborate procedures for quality control of auditor services; measures to stimulate staff of auditing entities to scrutinize requirements to implementation of the quality control system; obligating documents of auditing firms on assessment of ethical threats; sharing of duties among assignment group members; requirements to qualification of the key partner, quality controller; identification of auditor assignments; solutions of complicated issues and their documenting, measures on control of the assignment at the final phase and quality control of the assignment. The proposed measures are supposed to help auditing entities revise the already operating quality control systems in a timely manner, which will facilitate supply of high quality information to all the users of auditing reports, external quality controllers from the Body of Public Supervision over Auditing and the Auditor Chamber of Ukraine.

Automation Platform for CAR-T Manufacturing: The Benefits and the Clinical Outcomes

Background The development of chimeric antigen receptor (CAR) T cell therapy has shown tremendous success in the past decade. Since the first two autologous CD19-targeting CAR-T treatments, Kymriah and Yescarta, were approved by the FDA, the research activities in this field are being significantly increased. However, the scientific and clinical efforts have been extensively focused on developing novel CAR-T treatments with better tumour control or reduced on-target off tumor cytotoxicity. The importance of CAR-T manufacturing optimization has been relatively underestimated. It has been reported by FDA that Kymriah has about 9 % of manufacturing failure rate. This failure could directly affect the survival of some patients. Accordingly, some of the patients were forced to received out-of-spec product, because of the limited time window for another manufacturing attempt. The goal of this study is to examine if the qualities and consistency of the CAR-T products could be improved by an automatic manufacturing process. Methods Major CAR-T manufacturing variabilities resulted from the manual processing steps. To address the issues, we have adapted CliniMACS Prodigy (Miltenyi Biotec, Bergisch Gladbach, Germany), an all-in-one, automatic and closed system for cell processing, for our CAR-T manufacturing. In this study, we have compared the differences of CAR-T product from manual and automated processes, including the cell viability, transduction efficiency, and cell subset distribution. The in vitro cytotoxic effects of CAR-T cells made manually and automatically were also conducted by incubating the CAR-T cells with Raji cells at effector to target ratio (E:T) from 3:1 to 1:3. In order to test the inter-Prodigy variability, we applied the PBMC sample from one individual patient into two devices, and compared the quality indexes for the final products. Finally, we have performed a POC (proof of concept) CD19-CAR-T trials, and 3 patients who received CD19-CAR-T cells manufactured by CliniMACS Prodigy were evaluated. Results The comparisons between CAR-T cells from two manufacturing processes (n=6) suggested that the CAR-T cells made by Prodigy had significantly greater cell viability (Fig. 1a), higher transduction efficiency (Fig. 1b), and lower variations of cell subset distribution (Fig. 1c). It also showed that the Prodigy-made CAR-T cells had statistically higher in vitro cytotoxicity against Raji cells (Fig. 1d), possibly benefited from its higher transduction efficiency of CD19-CAR. The result of inter-Prodigy comparisons (Fig. 2), including final quality control indexes and the percentage of cell subset of the intermediate and final products, were almost identical. Since January 2018, 30 patients (one MCL, four DLBCL, and 25 B-ALL) have been treated with our FMC63-based or humanized FMC63-based CD19-CAR-T cells (Fig. 3). Among these patients, 28/30 (93.3%) cases achieved MRD-negative completed remission (CR), and two cases reached partial remission (PR) after receiving CAR-T infusion. All of the three patients who received automated-manufactured CAR-T cells (Fig 3, highlighted in yellow) have achieved CR in less than 20 days and have no sign of relapse until last follow-up date. Conclusions Compared to traditional small molecule drugs or biologics, the manufacturing successful rate for autologous CAR-T cells is much more critical because each failure could be live-threatening. Our comparison studies have proved that the automated process exhibited improved qualities and consistencies of CAR-T products. Moreover, automatic process will not only increase the manufacturing stability, but significantly reduce the dependency on qualified technicians or scientists, which will greatly prompt the commercialization of CAR-T cell products. Disclosures No relevant conflicts of interest to declare.