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Prediction of B cell epitopes that can replace the antigen for antibody production and detection is of great interest for research and the biotech industry. Here, we developed a novel BLAST-based method to predict linear B cell epitopes. To that end, we generated a BLAST-formatted database upon a dataset of 62,730 known linear B cell epitope sequences and considered as a B cell epitope any peptide sequence producing ungapped BLAST hits to this database with identity ≥ 80% and length ≥ 8. We examined B cell epitope predictions by this method in tenfold cross-validations in which we considered various types of non-B cell epitopes, including 62,730 peptide sequences with verified negative B cell assays. As a result, we obtained values of accuracy, specificity and sensitivity of 72.54 ± 0.27%, 81.59 ± 0.37% and 63.49 ± 0.43%, respectively. In an independent dataset incorporating 503 B cell epitopes, this method reached accuracy, specificity and sensitivity of 74.85%, 99.20% and 50.50%, respectively, outperforming state-of-the-art methods to predict linear B cell epitopes. We implemented this BLAST-based approach to predict B cell epitopes at http://imath.med.ucm.es/bepiblast .

CD8+ T cell immune monitoring aims at measuring the size and functions of antigen-specific CD8+ T cell populations, thereby providing insights into cell-mediated immunity operational in a test subject. The selection of peptides for ex vivo CD8+ T cell detection is critical because within a complex antigen exists a multitude of potential epitopes that can be presented by HLA class I molecules. Further complicating this task, there is HLA class I polygenism and polymorphism which predisposes CD8+ T cell responses towards individualized epitope recognition profiles. In this study, we compare the actual CD8+ T cell recognition of a well-characterized model antigen, human cytomegalovirus (HCMV) pp65 protein, with its anticipated epitope coverage. Due to the abundance of experimentally defined HLA-A * 02:01-restricted pp65 epitopes, and because in silico epitope predictions are most advanced for HLA-A * 02:01, we elected to focus on subjects expressing this allele. In each test subject, every possible CD8+ T cell epitope was systematically covered testing 553 individual peptides that walk the sequence of pp65 in steps of single amino acids. Highly individualized CD8+ T cell response profiles with aleatory epitope recognition patterns were observed. No correlation was found between epitopes’ ranking on the prediction scale and their actual immune dominance. Collectively, these data suggest that accurate CD8+ T cell immune monitoring may necessitate reliance on agnostic mega peptide pools, or brute force mapping, rather than electing individual peptides as representative epitopes for tetramer and other multimer labeling of surface antigen receptors.

It now seems to be a given that the principles that presided over the birth of liberalism and capitalism are no longer relevant. To understand the evolution of this ideology and economic system, Liberalism and Capitalism Today examines the work of the two authors who have contributed the most to the analysis of the conditions that lead to the emergence of these types of organization: Alexis de Tocqueville of France and Max Weber of Germany. This book thus analyzes how the evolution of the general environment of a civilization leads to the emergence of new ways of approaching economic life, and then to its development, thanks to innovations in many fields. This historical perspective makes it possible to understand the transformations that liberalism and capitalism could offer. It suggests a potential path that does not involve simply returning to a way of life that has been totally altered by the evolution of civilizations and the economy, but instead leads to a more peaceful way of living in most countries of the world.

SARS-CoV-2 infection takes a mild or clinically inapparent course in the majority of humans who contract this virus. After such individuals have cleared the virus, only the detection of SARS-CoV-2-specific immunological memory can reveal the exposure, and hopefully the establishment of immune protection. With most viral infections, the presence of specific serum antibodies has provided a reliable biomarker for the exposure to the virus of interest. SARS-CoV-2 infection, however, does not reliably induce a durable antibody response, especially in sub-clinically infected individuals. Consequently, it is plausible for a recently infected individual to yield a false negative result within only a few months after exposure. Immunodiagnostic attention has therefore shifted to studies of specific T cell memory to SARS-CoV-2. Most reports published so far agree that a T cell response is engaged during SARS-CoV-2 infection, but they also state that in 20-81% of SARS-CoV-2-unexposed individuals, T cells respond to SARS-CoV-2 antigens (mega peptide pools), allegedly due to T cell cross-reactivity with Common Cold coronaviruses (CCC), or other antigens. Here we show that, by introducing irrelevant mega peptide pools as negative controls to account for chance cross-reactivity, and by establishing the antigen dose-response characteristic of the T cells, one can clearly discern between cognate T cell memory induced by SARS-CoV-2 infection vs. cross-reactive T cell responses in individuals who have not been infected with SARS-CoV-2.

T cell immunity is traditionally assessed through functional recall assays, which detect the consequences of the T cells' antigen encounter, or via fluorescently labeled multimers that selectively bind peptide-specific T cell receptors. Using either approach, if the wrong antigen or peptide of a complex antigenic system, such as a virus, is used for immune monitoring, either false negative data will be obtained, or the magnitude of the antigen-specific T cell compartment will go largely underestimated. In this work, we show how selection of the \"right\" antigen or antigenic peptides is critical for successful T cell immune monitoring against human cytomegalovirus (HCMV). Specifically, we demonstrate that individual HCMV antigens, along with previously reported epitopes, frequently failed to detect CD8+ T cell immunity in test subjects. Through systematic assessment of T cell reactivity against individual nonamer peptides derived from the HCMVpp65 protein, our data clearly establish that (i) systematic testing against all potential epitopes encoded by the genome of the antigen of interest is required to reliably detect CD8+ T cell immunity, and (ii) genome-wide, large scale systematic testing of peptides has become feasible through high-throughput ELISPOT-based \"brute force\" epitope mapping.

The scope of immune monitoring is to define the existence, magnitude, and quality of immune mechanisms operational in a host. In clinical trials and praxis, the assessment of humoral immunity is commonly confined to measurements of serum antibody reactivity without accounting for the memory B cell potential. Relying on fundamentally different mechanisms, however, passive immunity conveyed by pre-existing antibodies needs to be distinguished from active B cell memory. Here, we tested whether, in healthy human individuals, the antibody titers to SARS-CoV-2, seasonal influenza, or Epstein–Barr virus antigens correlated with the frequency of recirculating memory B cells reactive with the respective antigens. Weak correlations were found. The data suggest that the assessment of humoral immunity by measurement of antibody levels does not reflect on memory B cell frequencies and thus an individual’s potential to engage in an anamnestic antibody response against the same or an antigenically related virus. Direct monitoring of the antigen-reactive memory B cell compartment is both required and feasible towards that goal.

We used four-color ImmunoSpot® assays, in conjunction with peptide pools that cover the sequence of tyrosinase (Tyr), melanoma-associated antigen A3 (MAGE-A3), melanocyte antigen/melanoma antigen recognized by T cells 1 (Melan-A/MART-1), glycoprotein 100 (gp100), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) to characterize the melanoma antigen (MA)-specific CD8 + cell repertoire in PBMC of 40 healthy human donors (HD). Tyr triggered interferon gamma (IFN-γ)-secreting CD8 + T cells in 25% of HD within 24 h of antigen stimulation ex vivo. MAGE-A3, Melan-A/MART-1, and gp100 also induced recall responses in 10%, 7.5%, and 2.5% of HD, respectively. At this time point, these CD8 + T cells did not yet produce GzB (granzyme B). However, they engaged in GzB production after 72 h of antigen stimulation. By this 72-h time point, 57.5% of the HD responded to at least one, and typically several, of the MA. A closer characterization of the Tyr-specific CD8 + T cell repertoire indicated that it was low-affinity, and to primarily entail a stem cell-like subpopulation. Collectively, our data reveal pre-existing endogenous T cell immunity against melanoma antigens in healthy donors, and analogous to natural autoantibodies, we have termed this “natural T cell autoreactivity”.

The required acceleration of onshore wind deployment requires the consideration of both economic and social criteria. With a spatially explicit analysis of the validated European turbine stock, we show that historical siting focused on cost-effectiveness of turbines and minimization of local disamenities, resulting in substantial regional inequalities. A multi-criteria turbine allocation approach demonstrates in 180 different scenarios that strong trade-offs have to be made in the future expansion by 2050. The sites of additional onshore wind turbines can be associated with up to 43% lower costs on average, up to 42% higher regional equality, or up to 93% less affected population than at existing turbine locations. Depending on the capacity generation target, repowering decisions and spatial scale for siting, the mean costs increase by at least 18% if the affected population is minimized — even more so if regional equality is maximized. Meaningful regulations that compensate the affected regions for neglecting one of the criteria are urgently needed.

The advent of the euro was a revolution for the 340 million people who exchanged their former currencies - considered a fundamental element of national sovereignty - for this new single currency.Encouraged by some who believe that its introduction gives more cohesion and strength to Europe in an increasingly globalized economy, the euro is criticized by others who believe that the constraints it imposes are a source of austerity and favor northern European countries at the expense of countries in the south.The Future of the Euro Currency traces the evolution of the monetary policy which the European Central Bank instituted at a time when economic, monetary and financial crises were legion. The book presents, as objectively as possible, the advantages and disadvantages of this new currency, while considering the improvements that could promote its durability.

A series of novel ionic liquids based on glucose was synthesized in high yields in simple two or three‐step reaction procedures. These carbohydrate‐based ionic liquids were studied and compared to commercially available imidazolium‐based ionic liquids as supports for Novozym 435 in the acrylation of n‐butanol. A direct correlation between the availability of hydroxy groups and the overall activity as well as an enhanced recyclability of the biocatalyst has been found for the glucose‐based ionic liquids. Biocatalysis, given its mild reaction conditions, is an important tool for the construction of acrylic esters, monomer assets in chemical industry, which are usually unstable against acids and heat. Several examples of ionic liquids were tested as supports for Novozym 435 in the construction of butyl acrylate Both a higher yield and a stable recyclability were found for the herein‐reported glucosylimidazolium‐based ionic liquids.