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Dysregulation of the epigenome drives aberrant transcriptional programmes that promote cancer onset and progression. Although defective gene regulation often affects oncogenic and tumour-suppressor networks, tumour immunogenicity and immune cells involved in antitumour responses may also be affected by epigenomic alterations. This could have important implications for the development and application of both epigenetic therapies and cancer immunotherapies, and combinations thereof. Here, we review the role of key aberrant epigenetic processes - DNA methylation and post-translational modification of histones - in tumour immunogenicity, as well as the effects of epigenetic modulation on antitumour immune cell function. We emphasize opportunities for small-molecule inhibitors of epigenetic regulators to enhance antitumour immune responses, and discuss the challenges of exploiting the complex interplay between cancer epigenetics and cancer immunology to develop treatment regimens combining epigenetic therapies with immunotherapies.

Vaccines against human papillomavirus (HPV) are available in Europe since 2006. They have been highly effective in preventing infection and disease caused by the vaccine types. Clinical efficacy data are available for cervical, vulvovaginal and anal precancer and invasive cervical cancer. Disease reduction is best with early vaccination and a coverage of more than 70%. Gender-neutral vaccination provides direct protection for all men and improves the coverage. A good coverage is followed by herd protection of the unvaccinated men and women. School-based programs appear to be most effective; under the age of 15 years, two doses with an interval of 6–12 months are sufficient. From the age of 15 years, the standard regimen with three doses is recommended. A broad catch-up program for young adult women and men improves the effectiveness. The vaccines are also effective in sexually active women and men with previous but cleared infections. Vaccination in addition to local treatment of HPV-related disease appears to reduce recurrent or subsequent HPV-related disease. Combination of HPV vaccination and screening with HPV testing is the most effective approach to prevention of cervical cancer. The screening intervals may increase in the vaccinated cohorts. The upper age limit for vaccination remains to be evaluated, is country specific and depends on cost-effectiveness. The European Society of Gynaecologic Oncology and the European Federation for Colposcopy strongly support gender-neutral vaccination programs for children and young adolescents, with a catch-up program for young adults. • Human papillomavirus (HPV) vaccination is highly effective in preventing cervical disease caused by the vaccine types. • It further reduces the burden of other HPV-related cancers, such as anal, oropharyngeal, vulvar and vaginal cancer. • School-based programs appear to be more cost-effective. • The vaccines have excellent safety profile. [ABSTRACT FROM AUTHOR]

Pain is a hallmark of tissue injury, inflammatory diseases, pathogen invasion and neuropathy. It is mediated by nociceptor sensory neurons that innervate the skin, joints, bones, muscles and mucosal tissues and protects organisms from noxious stimuli. Nociceptors are sensitized by inflammatory mediators produced by the immune system, including cytokines, lipid mediators and growth factors, and can also directly detect pathogens and their secreted products to produce pain during infection. Upon activation, nociceptors release neuropeptides from their terminals that potently shape the function of innate and adaptive immune cells. For some pathogens, neuron-immune interactions enhance host protection from infection, but for other pathogens, neuron-immune signalling pathways can be exploited to facilitate pathogen survival. Here, we discuss the role of nociceptor interactions with the immune system in pain and infection and how understanding these pathways could produce new approaches to treat infectious diseases and chronic pain.

Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers. [ABSTRACT FROM AUTHOR]

A few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against the virus cross-react with the tumor cells, we want to prompt clinical studies to evaluate the impact of SARS-CoV-2 infection on prognosis and follow up of various forms of tumors. These topics, including a brief historical overview, are discussed in this paper., (© 2021. The Author(s).)

The origin of beneficial mutations is fundamentally important in understanding the processes by which natural selection works. Using phage-resistant mutants in Escherichia coli as their model for identifying the origin of beneficial mutations, Luria and Delbrück distinguished between two different hypotheses. Under the first hypothesis, which they termed "acquired immunity," the phages induced bacteria to mutate to immunity; this predicts that none of the resistant mutants were present before infection by the phages. Under the second hypothesis, termed "mutation to immunity," resistant bacteria arose from random mutations independent of the presence of the phages; this predicts that resistant bacteria were present in the population before infection by the phages. These two hypotheses could be distinguished by calculating the frequencies at which resistant mutants arose in separate cultures infected at the same time and comparing these frequencies to the theoretical results under each model. The data clearly show that mutations arise at a frequency that is independent of the presence of the phages. By inference, natural selection reveals the genetic variation that is present in a population rather than inducing or causing this variation. [ABSTRACT FROM AUTHOR]

The complexity of the interconnected grid and the continuous increase of new energy sources have led to an acute problem with low‐frequency oscillation (LFO) in power system. Identification and monitoring of LFO in power grid are prerequisites for effective control of low‐frequency oscillation phenomena. To address matter that the traditional S‐transform time‐frequency window function has a fixed scale and cannot be applied to the specific local characteristics of different signals, an adaptive generalized S‐transform algorithm based on a bat algorithm is proposed in this paper. It uses adjustment parameters to control the generalized Gaussian window function. The parameters are automatically adjusted by a bat algorithm adaptive optimization to find the best time‐frequency characterization. Secondly, the PMU data waveform with implicit low‐frequency oscillation information is converted into a two‐dimensional time‐frequency figure including the onset moment, frequency, and amplitude. The system enables identification and visual monitoring of low‐frequency oscillations. After that, simulation experiments of New England system are conducted. The superiority of the proposed method is verified, which can greatly improve the time‐frequency resolution of PMU active power data signal and has effective noise immunity. [ABSTRACT FROM AUTHOR]

The suitability of blood collected on filter papers in comparison with corresponding conventional serum samples in the diagnosis of bovine anaplasmosis was studied using the Complement Fixation Test (CFT), DOT-ELISA, Western immunoblot and Rapid Card Agglutination Test (RCAT). Dried blood on Whatman filter paper no. 1 was eluted in 1.8 ml of PBS 0.05% Tween 20 given an initial dilution of 1:100. The reactivity in both DOT-ELISA and Western immunoblotting was similar to that obtained with the sera diluted 1:100. Filter paper samples gave lower reactivity in all the tests as compared with corresponding serum samples. There was no significant difference in the reactivity between the eluates from filter papers stored at room temperature and those stored at 4°C. Storage at room temperature did not significantly affect reactivity for up to 6 months. Eluates from filter papers stored for 6 months at room temperature continued to give similar reactivity to those from freshly prepared filter papers in both DOT-ELISA and Western blot, and in the Rapid Card Agglutination Test. It is concluded that collecting blood on filter papers is a suitable technique for large-scale screening and for seroepidemiological studies on anaplasmosis, and offers many advantages especially in developing countries where transport and cold chain facilities are a major constraint. [ABSTRACT FROM AUTHOR]

Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers. [ABSTRACT FROM AUTHOR]

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant-free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)-restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell-penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor-specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat 12.5 nanofiber) increased antigen cross-presentation by bone marrow-derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat 12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat 12.5 nanofibers exhibited increased presentation of the H2kb-epitope (reminiscent for cross-presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat 12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat 12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor-infiltrating IFN-γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber-based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response., (© 2020 Wiley Periodicals LLC.)

Prospective authors are requested to submit new, unpublished manuscripts for inclusion in the upcoming event described in this call for papers. [ABSTRACT FROM AUTHOR]

Psoriasis (PS) and atopic dermatitis (AD) are common inflammatory skin diseases characterized by an imbalance in specific T-cell subsets, resulting in a specific cytokine profile in patients. Obtaining models closely resembling both pathologies along with a relevant clinical impact is crucial for the development of new therapies because of the high prevalence of these diseases. Single-gene mouse models developed until now do not fully reflect the complexity of these disorders, in part not only because of inherent differences between mice and humans but also because of the multifactorial nature of these pathologies. The skin-humanized mouse model developed by our group, based on a tissue engineering approach, has been used to test therapeutic strategies, although this methodology is still technically challenging and not widely available. The skin-humanized mouse models for PS and AD reproduce human skin phenotypes, providing valuable tools for drug development and testing in the preclinical setting. The tissue engineering approach allows the development of personalized medicine, covering the broad genotypic spectrum of these pathologies. This review highlights the main differences between available murine models focusing on the tissue-specific immunity of PS and AD. We discuss their contribution to unravel the complex pathophysiology of these diseases and to translate this knowledge into more accurate therapies., (© 2020 Australian and New Zealand Society for Immunology Inc.)

Identifying the genetic architecture underlying phenotypic variation in natural populations and assessing the consequences of polymorphisms for individual fitness are fundamental goals in evolutionary and molecular ecology. Consistent between-individual differences in behaviour have been documented for a variety of taxa. Dissecting the genetic basis of such behavioural differences is however a challenging endeavour. The molecular underpinnings of natural variation in aggression remain elusive. Here, we used comparative gene expression (transcriptome analysis and RT-PCR), genetic association analysis and pharmacological experiments to gain insight into the genetic basis of aggression in wild-caught jumping spiders (Portia labiata). We show that spider aggression is associated with a putative viral infection response gene, BTB/POZ domain-containing protein 17 (BTBDH), in addition to a putative serotonin receptor 1A (5-HT1A) gene. Spider aggression varies with virus loads, and BTBDH is upregulated in docile spiders and exhibits a genetic variant associated with aggression. We also identify a putative serotonin receptor 5-HT1A gene upregulated in docile P. labiata. Individuals that have been treated with serotonin become less aggressive, but individuals treated with a nonselective serotonin receptor antagonist (methiothepin) also reduce aggression. Further, we identify the genetic variants in the 5-HT1A gene that are associated with individual variation in aggression. We therefore conclude that co-evolution of the immune and nervous systems may have shaped the between-individual variation in aggression in natural populations of jumping spiders., (© 2020 John Wiley & Sons Ltd.)

Recent studies support the notion that glycolysis and oxidative phosphorylation are rheostats in immune cells whose bioenergetics have functional outputs in terms of their biology. Specific intrinsic and extrinsic molecular factors function as molecular potentiometers to adjust and control glycolytic to respiratory power output. In many cases, these potentiometers are used by influenza viruses and immune cells to support pathogenesis and the host immune response, respectively. Influenza virus infects the respiratory tract, providing a specific environmental niche, while immune cells encounter variable nutrient concentrations as they migrate in response to infection. Immune cell subsets have distinct metabolic programs that adjust to meet energetic and biosynthetic requirements to support effector functions, differentiation, and longevity in their ever-changing microenvironments. This review details how influenza coopts the host cell for metabolic reprogramming and describes the overlap of these regulatory controls in immune cells whose function and fate are dictated by metabolism. These details are contextualized with emerging evidence of the consequences of influenza-induced changes in metabolic homeostasis on disease progression., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The 1996 Act has completed its quarter-century cycle of existence. At the time of its enactment, it was praised by scholars and practitioners as a “masterful… comprehensive” piece of legislation and one that was destined to “enhance the attractiveness of England as an arbitral forum”. These predictions proved exceedingly accurate. However, over time the legislation’s various shortcomings began to surface. Itsreview by the Law Commission was, therefore, very timely. This paper considersthe present state of English arbitration lawconsidering the provisions ofthe 1996Act and substantive and/or noteworthy recommendations proposed to the legislation, alongside the relevant case-law, and considers the appropriateness and potential utility of these recommendations. In particular, this article considers the following issues: the governing law of an arbitration agreement, the arbitrators’ duty of disclosure,theirimmunity from liability,the summary disposal of claims and defences,the confidentiality of arbitration and court powersin support of arbitral proceedings and emergency arbitrations. The paper concludesthat although the reform proposals are mostly commendable and sufficient to satisfy users’ concerns and expectations, not all are agreeable. Reform proposals do not go far enough. Most notably, the rule concerning the arbitrators’ duty of disclosure should recognise that, in appropriate instances, the subjective expectations of the parties should be addressed in the assessment. The parties’ reasonable and/or legitimate expectations should not be ignored when deciding what facts and circumstances to disclose to ensure that the partiesretain confidence in the process and remain the ultimate arbiters of their dispute. [ABSTRACT FROM AUTHOR]

Abstract: To compare immunologic phenotypes between (1) hepatocellular carcinoma (HCC) patients and a healthy population and (2) more advanced and early stage HCC patients, we studied 45 HCC patients and 46 healthy controls from January 2006 to January 2008. Using fluorescent activated cell sorter (FACS) analysis, HCC patients were demonstrated to exhibit stronger phagocytosis of granulocytes and monocytes and more peripheral blood mononuclear cells (PBMCs) in the G2/M phase compared with healthy volunteers. By contrast, lower percentages of B and Th lymphocytes were also found in the peripheral blood of HCC patients than in the healthy population. Most importantly, a higher percentage of B cells was found in patients with advanced HCC than in those with early HCC in terms of TNM stage (II and III vs I, p = 0.004), the Japanese Integrated Scoring system (2–3 vs 0–1, p = 0.0235), and tumor numbers (≥2 vs 1, p = 0.005). In conclusion, our findings suggested that HCC patients might exhibit enhanced innate immunity and reduced adaptive immunity compared with healthy volunteers. A higher percentage of B cells was found in patients with more advanced HCC compared with patients with early stage HCC, which might serve as an indicator of the severity of HCC. [Copyright &y& Elsevier]

Major studies are still lacking on the impact of differing intensities of long-term donor plasmapheresis, not only on total serum protein, albumin and immunoglobulin G (IgG), but also on humoral and cellular immunity, red cell and iron metabolism, and biochemical cardiovascular risk markers. Three groups of donors, comprising 483 individuals undergoing differing intensities of long-term serial plasmapheresis, were entered into a cross-sectional study. A fourth control group consisted of 100 non-donors. In addition to measuring total protein, albumin and IgG levels, we determined parameters of humoral and cellular immunity, red cell and iron metabolism and recognized biochemical cardiovascular risk factors. The median annual net amount of plasma donated by the three donor groups was 37, 16 and 10 l, respectively ( P < 0·0001). Donors had significantly lower total serum protein, albumin and IgG levels than non-donors ( P < 0·0001), but the intensity of plasmapheresis had no influence on those parameters. Like non-donors, all plasma donors had normal humoral and cellular immunity. No increased rates of iron store depletion were observed in the three groups of plasma donors. Plasma donors were not at increased cardiovascular risk. Regular donor plasmapheresis of up to 45 l of plasma per year appears to be as safe as more moderate plasmapheresis programmes, with respect to the parameters analysed in this study. Individuals donating under these conditions did not develop impaired humoral and cellular immunity, iron store depletion, or increased cardiovascular risk with regard to established biochemical risk markers. Prospective studies are required to determine more exactly than in retrospective analyses the reasons why donors withdraw from plasmapheresis programmes. [ABSTRACT FROM AUTHOR]

The 48 G>C transversion in exon 1 of the RHCE gene leads to Trp16Cys, usually present in the conventional RHCE Ce, while Trp16 is associated with RHCE ce. The presence of Cys16 in RHCE ce is associated with the R0 (Dce) haplotype in Africans, leading to a weak ‘e’ antigen expression on red blood cells (RBCs). VS is a common red cell antigen in individuals of African descent and results from a single point mutation in exon 5 of the RHCE (733C>G), leading to Leu245Val substitution; VS positivity is also associated with weak expression of ‘e’. This study investigated the association of Cys16 and/or VS with the RHCE ce alleles in a cohort of sickle cell disease (SCD) patients phenotyped as R0r or R0R0 and rr. DNA samples from 58 SCD patients were tested for the 48 G>C transversion, encoding Cys16, by allele-specific polymerase chain reaction (PCR). We also amplified exon 5 of the RHCE by PCR and subjected the amplified product to restriction fragment length polymorphism analysis, using BfaI, in order to determine the VS status. Further cDNA analysis was performed on three samples to verify whether the mutations were located on the same or on different alleles. Fifty-six of the 58 SCD patients studied (97%) were heterozygous for 48G/48C (Cys16). Of these, 18 (32%) were also heterozygous for 733C/G (245Val). All of these 18 samples showed weak ‘e’ expression on RBCs when tested with at least one monoclonal antibody to e antigen. cDNA sequencing of three of 18 patient samples showed that the genes encoding Cys16 and Val245 (VS) were on different alleles. We found a high incidence of Cys16 associated with the RHCE ce in our SCD cohort. A high percentage of these patients were also found to be heterozygous for VS. cDNA analysis showed that, in at least three samples, the two mutations were on different alleles, with consequent weakening of expression of the e antigen on RBCs. [ABSTRACT FROM AUTHOR]

The adaptive immune system is tasked with producing antibodies that recognize a wide scope of potential pathogens, including those never before encountered, and concurrently avoiding formation of antibodies binding host tissues. The diverse repertoire of antibodies produced by V(D)J recombination inevitably includes autoantibodies that bind to self-antigens, estimated to be as much as 70% of nascent antibodies on immature B cells. Early theoretical models of tolerance hypothesized that such self-reactive clones could not possibly be allowed to survive and mature. However from the first direct view of the fate of nascent B cells carrying a self-binding antibody it was clear that many "forbidden clones" circulate to secondary lymphoid tissues, where they adopt an IgM low IgD+ cell surface phenotype and are prevented from secreting autoantibodies by a series of tolerance checkpoints referred to as "clonal anergy." Since anergic B cells can be reactivated to secrete pathogenic autoantibodies in certain settings, the advantage of controlling self-reactive antibodies by clonal anergy has until recently remained enigmatic. Here we review this topic and recent advances showing that anergic B cells are recruited into the germinal center to mutate away from self-reactivity, undergoing "clonal redemption" into cells making antibodies with exquisite specificity for foreign immunogens., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction and aim. Sleep is a complex physiological process important for body homeostasis. Sleep and sleep deprivation have been shown to have a significant impact on mental health and psychoneuroimmunology. Sleep deprivation also can lead to an increased susceptibility to infections and other illnesses. Moreover, sleep is crucial for the maintenance of emotional, cognitive, and behavioral functions. Material and methods. A systematic search of the literature (clinical trials and reviews) published in the last five years was performed using PubMed/MEDLINE and Embase. Survey research (n= 555: 404 women and 151 men in the age range 15-30, 23 questions in total) was also conducted by the authors of this study. Analysis of literature. Literature data indicate a decline in immune function caused by sleep deprivation. In addition, a number of mental health problems such as depression and anxiety were caused by sleep disorders. What's more, there is a strong link between the glymphatic system and brain detoxification during sleep. As many as 47% of our respondents noticed a decrease in immunity during periods of sleep deprivation. Immunity is one of the 4 most frequently mentioned factors by respondents that can be affected by lack of sleep. Conclusion. Sleep and sleep deprivation affect mental health and immune responses. Adequate sleep is essential for maintaining optimal health, and addressing sleep problems may help prevent or manage mental health disorders and immune- related diseases. [ABSTRACT FROM AUTHOR]

Nutrition may affect animal health due to the strong link between them. Also, diets improve the healing process in various disease states. Cancer is a disease, where the harmful consequences of tumors severely impair the body. The information regarding the evolution of this disease is extrapolated from human to animal because there are few specific studies regarding nutritional needs in animals with cancer. Thus, this paper aims to review the literature regarding the immunomodulatory effects of vitamins in mammal cancer. An adequate understanding of the metabolism and requirements of nutrients for mammals is essential to ensuring their optimal growth, development, and health, regardless of their food sources. According to these: 1) Some species are highly dependent on vitamin D from food, so special attention must be paid to this aspect. Calcitriol/VDR signaling can activate pro-apoptotic proteins and suppress antiapoptotic ones. 2) Nitric oxide (NO) production is modulated by vitamin E through inhibiting transcription nuclear factor kappa B (NF-kB) activation. 3) Thiamine supplementation could be responsible for the stimulation of tumor cell proliferation, survival, and resistance to chemotherapy. 4) Also, it was found that the treatment with NO-Cbl in dogs is a viable anti-cancer therapy that capitalizes on the tumor-specific properties of the vitamin B12 receptor. Therefore, diets should contain the appropriate class of compounds in adequate proportions. Also, the limitations of this paper are that some vitamins are intensively studied and at the same time regarding others, there is a lack of information, especially in animals. Therefore, some subsections are longer and more heavily debated than others. [ABSTRACT FROM AUTHOR]

Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role in disease occurrence and progression, and different PCD-related genes have the potential to be targeted for the treatment of sepsis. In this paper, we analyzed PCD-related genes in sepsis. Implicated PCD processes include apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, and alkaliptosis. We screened for diagnostic-related genes and constructed models for diagnosing sepsis using multiple machine-learning models. In addition, the immune landscape of sepsis was analyzed based on the diagnosis-related genes that were obtained. In this paper, 10 diagnosis-related genes were screened for using machine learning algorithms, and diagnostic models were constructed. The diagnostic model was validated in the internal and external test sets, and the Area Under Curve (AUC) reached 0.7951 in the internal test set and 0.9627 in the external test set. Furthermore, we verified the diagnostic gene via a qPCR experiment. The diagnostic-related genes and diagnostic genes obtained in this paper can be utilized as a reference for clinical sepsis diagnosis. The results of this study can act as a reference for the clinical diagnosis of sepsis and for target discovery for potential therapeutic drugs. [ABSTRACT FROM AUTHOR]

Background: Lewis serologic reagents frequently give inaccurate phenotyping results. Furthermore these serologic reagents are often used in nonserologic assays such as inhibition and immunohistochemistry. In both scenarios knowledge of the fine specificity and cross-reactivity of these reagents will improve the quality of results obtained.Study Design and Methods: A range of contemporary and historical workshop and developmental Lewis reagents including mouse monoclonal (MoAb) and human and goat polyclonal (PoAb) reagents were evaluated. All were evaluated both against Lewis kodecytes expressing only single Le(a) , Le(b) , ALe(b) , BLe(b) , Le(x) , Le(y) , ALe(y) , or BLe(y) antigens and against the same antigens inkjet printed on a paper-based microplate and analyzed by enzyme immunoassay. Nine clinical samples were also evaluated. A kodecyte antigen dilution sensitivity assay was used to establish the ratio of Le(b) antigen between group A1 /A2 and O RBCs.Results: A continuum of cross-reactivity from Le(x) through to H was observed with MoAbs. All PoAb and few MoAb anti-Le(a) samples and reagents cross-reacted to some degree with Le(b) antigen. Some PoAb and MoAb anti-Le(b) did not cross-react with Le(a) . All polyclonal goat anti-Le(b) reagents showed substantial activity against ALe(b) and BLe(b) , while no MoAb reagent had this activity. A1 RBCs had less than half the Le(b) antigen of A2 /O RBCs.Conclusions: Substantial cross-reactivity of both MoAbs and PoAbs with related antigens highlights the risks of using serologic reagents in nonserologic assays or against synthetic antigens. The lack of ALe(b) activity in anti-Le(b) MoAbs explains their poor performance against blood group A1 Le(a-b+) phenotypes. [ABSTRACT FROM AUTHOR]

This paper studies continuing optimal lockdowns (can also be interpreted as quarantines or self-isolation) in the long run if a disease (Covid-19) is endemic and immunity can fail, that is, the disease has SIRS dynamics. We model how disease related mortality affects the optimal choices in a dynamic general equilibrium neoclassical growth framework. An extended welfare function that incorporates loss from mortality is used. In a disease endemic steady state, without this welfare loss even if there is continuing mortality, it is not optimal to impose even a partial lockdown. We characterize how the optimal restriction and equilibrium outcomes vary with the effectiveness of the lockdown, the productivity of working from home, the rate of mortality from the disease, and failure of immunity. We provide the sufficiency conditions for economic models with SIRS dynamics with disease related mortality–a class of models which are non-convex and have endogenous discounting so that no existing results are applicable. [ABSTRACT FROM AUTHOR]