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Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021.As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented.Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030).The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).

Noninvasive blood pressure measurements are less accurate than direct measurements but arterial catheterization for direct blood pressure monitoring can be challenging especially in patients with a nonpalpable pulse. The purpose of this study is to describe a novel technique of locating the dorsal pedal arterial pulse using a portable ultrasonic Doppler for arterial catheter placement.Using the described technique in anesthetized dogs and cats with strong (n = 13) to weak dorsal pedal pulses (n = 6), the overall success rate of arterial puncture was 70% (19/27) with successful catheterization in 53% (10/19) of those. The overall success rate of arterial catheterization was 37% (10/27). The pulse strength did not significantly affect the success rate. Neither were patient weight, blood pressure, heart rate, and premedication significantly different between the 2 groups.This study describes a novel technique for locating the dorsal pedal artery for arterial catheterization. Having another technique of pulse detection may increase the likelihood of arterial catheter placement for direct blood pressure monitoring and aid in arterial puncture for obtaining a sample for blood gas analysis in critical patients.

Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.

Purpose To explain the new U.S. Securities and Exchange Commission (“SEC”) Rule 2a-5 (the “Fair Value Rule”) under the Investment Company Act of 1940 (the “1940 Act”), which addresses the valuation practices of registered investment companies and business development companies. Design/methodology/approach Provides an overview of the Fair Value Rule, followed by a more detailed summary of the key provisions, including relevant guidance provided by the SEC in the release adopting the Fair Value Rule. Findings The Fair Value Rule establishes a specific framework, a standard of baseline practices across funds, and a set of required functions that must be performed in order to determine in good faith the fair value of a fund’s investments for purposes of applying Section 2(a)(41) of the 1940 Act. Originality/value Practical guidance from experienced investment management lawyers.

Background The MNS blood group system is defined by three homologous genes: GYPA, GYPB, and GYPE. GYPB encodes for glycophorin B (GPB) carrying S/s and the "universal" antigen U. RBCs of approximately 1% of individuals of African ancestry are U- due to absence of GPB. The U- phenotype has long been attributed to a deletion encompassing GYPB exons 2 to 5 and GYPE exon 1 (GYPB*01N). Study design and methods Samples from two U-individuals underwent Illumina short read whole genome sequencing (WGS) and Nanopore long read WGS. In addition, two existing WGS datasets, MedSeq (n = 110) and 1000 Genomes (1000G, n = 2535), were analyzed for GYPB deletions. Deletions were confirmed by Sanger sequencing. Twenty known U- donor samples were tested by a PCR assay to determine the specific deletion alleles present in African Americans. Results Two large GYPB deletions in U- samples of African ancestry were identified: a 110 kb deletion extending left of GYPB (DEL_B_LEFT) and a 103 kb deletion extending right (DEL_B_RIGHT). DEL_B_LEFT and DEL_B_RIGHT were the most common GYPB deletions in the 1000 Genomes Project 669 African genomes (allele frequencies 0.04 and 0.02). Seven additional deletions involving GYPB were seen in African, Admixed American, and South Asian samples. No samples analyzed had GYPB*01N. Conclusions The U- phenotype in those of African ancestry is primarily associated with two different complete deletions of GYPB (with intact GYPE). Seven additional less common GYPB deletion backgrounds were found. GYPB*01N, long assumed to be the allele commonly encoding U- phenotypes, appears to be rare.

The cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Cohesin is a ring complex composed of four core subunits and seven regulatory subunits. In an effort to comprehensively identify additional cohesin-interacting proteins, we used gene editing to introduce a dual epitope tag into the endogenous allele of each of 11 known components of cohesin in cultured human cells, and we performed MS analyses on dual-affinity purifications. In addition to reciprocally identifying all known components of cohesin, we found that cohesin interacts with a panoply of splicing factors and RNA-binding proteins (RBPs). These included diverse components of the U4/U6.U5 tri-small nuclear ribonucleoprotein complex and several splicing factors that are commonly mutated in cancer. The interaction between cohesin and splicing factors/RBPs was RNA- and DNA-independent, occurred in chromatin, was enhanced during mitosis, and required RAD21. Furthermore, cohesin-interacting splicing factors and RBPs followed the cohesin cycle and prophase pathway of cell cycle–regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors and RBPs resulted in aberrant mitotic progression. These results provide a comprehensive view of the endogenous human cohesin interactome and identify splicing factors and RBPs as functionally significant cohesin-interacting proteins.

Background and Objectives: Non-invasive assays for predicting foetal blood group status in pregnancy serve as valuable clinical tools in the management of pregnancies at risk of detrimental consequences due to blood group antigen incompatibility. To secure clinical applicability, assays for non-invasive prenatal testing of foetal blood groups need to follow strict rules for validation and quality assurance. Here, we present a multi-national position paper with specific recommendations for validation and quality assurance for such assays and discuss their risk classification according to EU regulations. Materials and Methods: We reviewed the literature covering validation for in-vitro diagnostic (IVD) assays in general and for non-invasive foetal RHD genotyping in particular. Recommendations were based on the result of discussions between co-authors. Results: In relation to Annex VIII of the In-Vitro-Diagnostic Medical Device Regulation 2017/746 of the European Parliament and the Council, assays for non-invasive prenatal testing of foetal blood groups are risk class D devices. In our opinion, screening for targeted anti-D prophylaxis for non-immunized RhD negative women should be placed under risk class C. To ensure high quality of non-invasive foetal blood group assays within and beyond the European Union, we present specific recommendations for validation and quality assurance in terms of analytical detection limit, range and linearity, precision, robustness, pre-analytics and use of controls in routine testing. With respect to immunized women, different requirements for validation and IVD risk classification are discussed. Conclusion: These recommendations should be followed to ensure appropriate assay performance and applicability for clinical use of both commercial and in-house assays. (Less)

Adaptive immunity can target a nearly infinite range of antigens, yet it is tempered by tolerogenic mechanisms that limit autoimmunity. Such immunological tolerance, however, creates a gap in adaptive immunity against microbes decorated with self-like antigens as a form of molecular mimicry. Our results demonstrate that the innate immune lectin galectin-7 (Gal-7) binds a variety of distinct microbes, all of which share features of blood group-like antigens. Gal-7 binding to each blood group expressing microbe, including strains of

Emm is a high incidence red cell antigen with eight previously reported Emm− probands. Anti-Emm appears to be naturally occurring yet responsible for a clinically significant acute hemolytic transfusion reaction. Previous work suggests that Emm is located on a GPI-anchored protein, but the antigenic epitope and genetic basis have been elusive. We investigated samples from a South Asian Indian family with two Emm− brothers by whole genome sequencing (WGS). Additionally, samples from four unrelated Emm− individuals were investigated for variants in the candidate gene. Filtering for homozygous variants found in the Emm− brothers and by gnomAD frequency of PIGG [NM_001127178.3:c.2624_2625delTA, p.(Leu875*), rs771819481]. PIGG encodes for a transferase, GPI-ethanolaminephosphate transferase II, which adds ethanolamine phosphate (EtNP) to the second mannose in a GPI-anchor. The four additional unrelated Emm− individuals had various PIGG mutations; deletion of Exons 2–3, deletion of Exons 7–9, insertion/deletion (indel) in Exon 3, and new stop codon in Exon 5. The Emm− phenotype is associated with a rare deficiency of PIGG, potentially defining a new Emm blood group system composed of EtNP bound to mannose, part of the GPI-anchor. The results are consistent with the known PI-linked association of the Emm antigen, and may explain the production of the antibody in the absence of RBC transfusion. Any association with neurologic phenotypes requires further research.

Cohesin is a multiprotein ring complex that regulates 3D genome organization, sister chromatid cohesion, gene expression, and DNA repair. Cohesin is known to be ubiquitinated, although the mechanism, regulation, and effects of cohesin ubiquitination remain poorly defined. We previously used gene editing to introduce a dual epitope tag into the endogenous allele of each of 11 known components of cohesin in human HCT116 cells. Here we report that mass spectrometry analysis of dual-affinity purifications identified the USP13 deubiquitinase as a novel cohesin-interacting protein. Subsequent immunoprecipitation/Western blots confirmed the endogenous interaction in HCT116, 293T, HeLa, and RPE-hTERT cells; demonstrated that the interaction occurs specifically in the soluble nuclear fraction (not in the chromatin); requires the ubiquitin-binding domains (UBA1/2) of USP13; and occurs preferentially during DNA replication. Reciprocal dual-affinity purification of endogenous USP13 followed by mass spectrometry demonstrated that cohesin is its primary interactor in the nucleus. Ectopic expression and CRISPR knockout of USP13 showed that USP13 is paradoxically required for both deubiquitination and ubiquitination of cohesin subunits in human cells. USP13 was dispensable for sister chromatid cohesion in HCT116 and HeLa cells, whereas it was required for the dissociation of cohesin from chromatin as cells transit through mitosis. Together these results identify USP13 as a new cohesin-interacting protein that regulates the ubiquitination of cohesin and its cell cycle regulated interaction with chromatin.

Polysynthetic languages have exceptionally large and sparse vocabularies, thanks to the number of morpheme slots and combinations in a word. This complexity, together with a general scarcity of written data, poses a challenge to the development of natural language technologies. To address this challenge, we offer linguistically-informed approaches for bootstrapping a neural morphological analyzer, and demonstrate its application to Kunwinjku, a polysynthetic Australian language. We generate data from a finite state transducer to train an encoder-decoder model. We improve the model by “hallucinating” missing linguistic structure into the training data, and by resampling from a Zipf distribution to simulate a more natural distribution of morphemes. The best model accounts for all instances of reduplication in the test set and achieves an accuracy of 94.7% overall, a 10 percentage point improvement over the FST baseline. This process demonstrates the feasibility of bootstrapping a neural morph analyzer from minimal resources.

BACKGROUND: Although P1 and Xg(a) are known to be associated with the A4GALT and XG genes respectively, the genetic basis of antigen expression has been elusive. Recent reports link both P1 and Xg(a) expression with nucleotide changes in the promotor regions and with antigen negative phenotypes due to disruption of transcription factor binding. STUDY DESIGN AND METHODS: Whole genome sequencing was performed on 113 individuals as part of the MedSeq Project with serologic RBC antigen typing for P1 (n=77) and Xg(a) (n=15). Genomic data were analyzed by two approaches, nucleotide frequency correlation or serologic correlation, to find A4GALT and XG changes associated with P1 and Xg(a) expression. RESULTS: For P1, the frequency approach identified 29 possible associated nucleotide changes, and the serologic approach revealed four among them correlating with the P1+/P1− phenotype: chr22:43,115,523_43,115,520AAAG/delAAAG (rs66781836); chr 22:43,114,551C/T (rs8138197); chr22:43,114,020T/G (rs2143918); and chr22:43,113,793G/T (rs5751348). For Xg(a), the frequency approach identified 82 possible associated nucleotide changes, and among these the serologic approach revealed one correlating with the Xg(a+)/Xg(a–) phenotype: chrX:2,666,384G/C (rs311103). CONCLUSION: A bioinformatics analysis pipeline was created to identify genetic changes responsible for RBC antigen expression. This study, in progress prior to the recently published reports, independently confirms the basis for P1 and Xg(a). Although, this enabled molecular typing of these antigens, the Y chromosome PAR1 region interfered with Xg(a) typing in males. This approach could be used to identify and confirm the genetic basis of antigens, potentially replacing the historical approach using family pedigrees as genomic sequencing becomes common place.

Summary Background There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh—the most important blood groups—cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. Methods This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis–trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons. Findings We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). Interpretation By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. Funding National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Purpose The purpose of this paper is to summarize and discuss the implications of three related U.S. Securities and Exchange Commission (SEC) no-action letters dated October 26, 2017 that seek to address the provisions of MiFID II related to “inducements”. Design/methodology/approach Provides background information regarding MiFID II and summarizes each of the three SEC Staff no-action letters: the SIFMA letter, the ICI letter and the AMG letter. Findings The no-action letters provide market participants with increased clarity as to how certain aspects of their business activities, in particular the “bundling” or “unbundling” of payments for research and execution, can comply with potentially competing systems of regulations. Originality/value Practical guidance from experienced financial industry and investment management lawyers.

In previous work we developed and implemented a sub-grid model for the efficient simulation of heat transfer in gas-particle flows around immersed horizontal cylinders. In this study we apply verification, validation, and uncertainty quantification methods to the developed model to rigorously examine its capabilities and limitations. Numerical verification with small, unit-cell problems shows excellent transient and steady-state behavior. Validation of a bubbling bed and a turbulent bed showed good agreement with high-resolution simulations. To quantify the error of the constitutive model predictions two methods were used to calculate confidence intervals, showing an error of approximately ± 20%, well within the range of typical Nusselt number approximations. The sub-grid model was applied to a conceptual pilot-scale 1 MWe carbon capture reactor to compare with alternative modeling methods. Results show fair predictions of hydrodynamics, heat transfer, and carbon capture rates with significant savings in computational runtimes.

The formation of dendrites on the anode surface of metal air batteries, such as the Li-air battery, causes significant decreases in performance over the lifetime of the battery and poses safety concerns due to short circuiting. Predictive computational methods are used to investigate novel electrolyte materials which will reduce dendrite growth, in particular liquid crystal materials for Li-air electrolytes. The literature on liquid crystal electrolytes was surveyed for materials data and used to develop a training set of liquid crystal compounds. These compounds were then used as a knowledge base to develop property structure relations for the clearing and melting temperature for liquid crystals, which are a critical design parameter for the design of novel electrolytes. This was accomplished using standard artificial neural networks trained on molecular fingerprints and convolutional neural networks (CNNs) trained on compound images. Transfer learning was also demonstrated to boost predictive performance through pre-training neural networks on larger pre-existing compound datasets. The results show that CNNs achieve comparable accuracy compared to molecular fingerprints, and that both multilayer perceptrons and CNNs can benefit from transfer learning. This study is the first where transfer learning in CNNs aids in the prediction of one experimental property in a small data regime, using data of another experimental property.

O artigo analisa a tradução de Isaías 52.15, particularmente, as diferenças de interpretação do termo יַזֶּה. As versões modernas divergem na tradução desse verbo, e essa divergência não se limita à terminologia, mas traz implicações ao próprio sentido da frase. Há pelo menos dois campos de sentido representados nas traduções: o primeiro corresponde a “borrifar”, “aspergir”; e o segundo, a “causar admiração”, “assombrar”, “causar espanto”. O argumento desenvolvido é o de que, para se interpretar essa passagem, precisa-se recorrer não apenas às evidências textuais, lexicais e gramaticais, mas também aos aspectos sintáticos e discursivos da unidade e seu contexto.

The apparatus of social reproduction describes the process by which knowledge production contributes to oppressive conditions. This article explains and defines this process through the application of a critical theoretical lens informed the Foucauldian concept of apparatus or dispositif and social reproduction as developed by feminist activists and intellectuals. This process has a notable influence on the political economic conditions of transgender women, conditions that include disproportionate reliance on the use of criminalized economies such as sex work. Social workers inadvertently influence this process through an overreliance on broad categorizations for lesbian, gay, bisexual, transgender, and queer populations, which impede our ability to adequately assess such complex oppressive social relationships. Increasing the profession’s familiarity and competence with critical theory is necessary to reduce our participation in such processes and identify effective interventions for this population. Presenting a review of social work literature and a discussion of the proposed lens, the following seeks to illuminate the apparatus of social reproduction and explain how broad social categorization of transgender women is problematic. The authors recommend the adoption of the proposed lens as a tool social workers can use to better assess their research and practice and better understand the complexities of power and exploitation.

In virtual design and scale up of pilot-scale carbon capture systems, the coupled reactive multiphase flow problem must be solved to predict the adsorber's performance and capture efficiency under various operation conditions. This paper focuses on the detailed computational fluid dynamics (CFD) modeling of a pilot-scale fluidized bed adsorber equipped with vertical cooling tubes. Multiphase Flow with Interphase eXchanges (MFiX), an open-source multiphase flow CFD solver, is used for the simulations with custom code to simulate the chemical reactions and filtered sub-grid models to capture the effect of the unresolved details in the coarser mesh for simulations with reasonable accuracy and manageable computational effort. Previously developed filtered models for horizontal cylinder drag, heat transfer, and reaction kinetics have been modified to derive the 2D filtered models representing vertical cylinders in the coarse-grid CFD simulations. The effects of the heat exchanger configurations (i.e., horizontal or vertical tubes) on the adsorber's hydrodynamics and CO2 capture performance are then examined. A one-dimensional three-region process model is briefly introduced for comparison purpose. The CFD model matches reasonably well with the process model while provides additional information about the flow field that is not available with the process model.

BACKGROUND:Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by autoantibodies that preferentially react at 4°C. Laboratory testing for cold-reactive autoantibodies is laborious and may not be ordered judiciously, particularly in patients with a negative direct antiglobuli