Predictive Power of a Bayesian Effective Action for Fully Connected One Hidden Layer Neural Networks in the Proportional Limit.

We perform accurate numerical experiments with fully connected one hidden layer neural networks trained with a discretized Langevin dynamics on the MNIST and CIFAR10 datasets. Our goal is to empirically determine the regimes of validity of a recently derived Bayesian effective action for shallow architectures in the proportional limit. We explore the predictive power of the theory as a function of the parameters (the temperature T, the magnitude of the Gaussian priors λ_{1}, λ_{0}, the size of the hidden layer N_{1}, and the size of the training set P) by comparing the experimental and predicted generalization error. The very good agreement between the effective theory and the experiments represents an indication that global rescaling of the infinite-width kernel is a main physical mechanism for kernel renormalization in fully connected Bayesian standard-scaled shallow networks.

COVID-19 Vaccine Hesitancy and Early Adverse Events Reported in a Cohort of 7,881 Italian Physicians.

Background: The COVID-19 vaccination campaign began in Italy at the end of December 2020, with the primary aim of immunizing healthcare professionals, using the EMA approved mRNA vaccines (Comirnaty® by Pfizer/BioNTech; mRNA-1273 by Moderna) and recombinant adenoviral vaccine (Vaxzevria® by AstraZeneca). The study aimed at evaluating the prevalence and motivations underlying Vaccine Hesitancy, as well as the incidence and type of adverse events associated with COVID-19 vaccination. Methods: Cross-sectional study. Data were collected January 1st to 28th 2021 using a purposely created online self-administered questionnaire from a selected cohort of Italian physicians. Results: Overall, 7,881 questionnaires were analyzed: 6,612 physicians had received one dose, and 1,670 two doses of Comirnaty®; 30 had received one dose of mRNA-1273. Vaccine Hesitancy rate was 3.6%; it correlated with prior SARS-CoV-2 infection, diabetes, Adverse Eventss at previous vaccinations and refusal of 2020 flu vaccine, and was mainly motivated by concerns about vaccine Adverse Events. Typical Adverse Events were pain/itching/paresthesia at the inoculation site, followed by headache, fever, fatigue and myalgia/arthralgia occurring more frequently after the second dose (77.8 vs 66.9%; p<0.001), and in subjects with a prior SARS-CoV-2 infection. Conclusion: Adherence to COVID-19 vaccination is high among physicians. Adverse Events are typically mild and more frequent in people with a prior SARS-CoV-2 infection.

Complex phase ordering of the one-dimensional Heisenberg model with conserved order parameter.

We study the phase-ordering kinetics of the one-dimensional Heisenberg model with conserved order parameter by means of scaling arguments and numerical simulations. We find a rich dynamical pattern with a regime characterized by two distinct growing lengths. Spins are found to be coplanar over regions of a typical size LV(t), while inside these regions smooth rotations associated to a smaller length LC(t) are observed. Two different and coexisting ordering mechanisms are associated to these lengths, leading to different growth laws LV(t) approximately t1/3 and LC(t) approximately t1/4 violating dynamical scaling.

Phase-ordering kinetics on graphs.

We study numerically the phase-ordering kinetics following a temperature quench of the Ising model with single spin-flip dynamics on a class of graphs, including geometrical fractals and random fractals, such as the percolation cluster. For each structure we discuss the scaling properties and compute the dynamical exponents. We show that the exponent a_{chi} for the integrated response function, at variance with all the other exponents, is independent of temperature and of the presence of pinning. This universal character suggests a strict relation between a_{chi} and the topological properties of the networks, in analogy to what is observed on regular lattices.

Universal features of information spreading efficiency on d-dimensional lattices.

A model for information spreading in a population of N mobile agents is extended to d-dimensional regular lattices. This model, already studied on two-dimensional lattices, also takes into account the degeneration of information as it passes from one agent to the other. Here, we find that the structure of the underlying lattice strongly affects the time tau at which the whole population has been reached by information. By comparing numerical simulations with mean-field calculations, we show that dimension d=2 is marginal for this problem and mean-field calculations become exact for d>2. Nevertheless, the striking nonmonotonic behavior exhibited by the final degree of information with respect to N and the lattice size L appears to be geometry independent.

Role and potential therapeutic use of antibodies against herpetic infections.

BACKGROUND: The cellular adaptive response directed against herpesviruses is widely described in the scientific literature as a pivotal component of the immune system able to control virus replication. The role of humoral immunity remains unclear and controversial. AIMS: Discussing the role of adaptive immunity in herpesvirus infection control, highlighting the potential role of the humoral branch of immunity through the description of human monoclonal antibodies directed against herpesviruses. SOURCES: PubMed search for relevant publications related to protective immunity against Herpesviridae. CONTENT: This review describes the role of adaptive immunity directed against Herpesviridae, focusing on the human humoral response naturally elicited during their infections. Given the ever-increasing interest in monoclonal antibodies as novel therapeutics, the contribution of humoral immunity in controlling productive infection, during both primary infection and reactivations, is discussed. IMPLICATIONS: Human monoclonal antibodies directed against the different Herpesviridae species may represent novel molecular probes to further characterize the molecular machinery involved in herpesvirus infection; and allow the development of novel therapeutics and effective vaccine strategies.

Efficiency of information spreading in a population of diffusing agents.

We introduce a model for information spreading among a population of N agents diffusing on a square L x L lattice, starting from an informed agent (Source). Information passing from informed to unaware agents occurs whenever the relative distance is < or = 1. Numerical simulations show that the time required for the information to reach all agents scales as N(-alpha)L(beta), where alpha and beta are noninteger. A decay factor z takes into account the degeneration of information as it passes from one agent to another; the final average degree of information of the population tau(av)(z) is thus history dependent. We find that the behavior of tau(av)(z) is nonmonotonic with respect to N and L and displays a set of minima. Part of the results are recovered with analytical approximations.

Topological filters and high-pass/low-pass devices for solitons in inhomogeneous networks.

We show that, by inserting suitable finite networks at a site of a chain, it is possible to realize filters and high-pass/low-pass devices for solitons propagating along the chain. The results are presented in the framework of coupled optical waveguides; possible applications to different contexts, such as photonic lattices and Bose-Einstein condensates in optical networks are also discussed. Our results provide a first step in the control of the soliton dynamics through the network topology.

A vector for the expression of recombinant monoclonal Fab fragments in bacteria.

The availability of genes coding for monoclonal Fab fragments of a desired specificity permits their expression in bacteria and provides a simple method for the generation of good quality reagents. In this paper we describe a new phagemid vector for the production of recombinant Fabs from genes obtained from phage display combinatorial libraries. The phagemid features an antibiotic resistance cassette which, once inserted between the heavy chain fragment and the light chain genes, avoids unwanted recombination and preserves useful restriction sites not affecting the Fab production rate.

Molecular profile of a human monoclonal antibody Fab fragment specific for Epstein-Barr virus gp350/220 antigen.

Experimental evidence indicates Epstein Barr virus (EBV) envelope glycoprotein gp350/220 elicits a potent virus neutralizing response in the infected human host that may play an important role in restricting viral pathogenesis. In this study, we report the molecular cloning in combinatorial phage display vectors, of the IgG1 repertoire of an individual naturally infected with EBV, and describe the recovery and characterization of a monoclonal antibody recognizing gp350/220. A detailed understanding of the human antibody response in EBV infection will identify antibodies of potential use in anti-viral prophylaxis and will advance the production of more effective vaccine candidates.

n--> infinity limit of O(n) ferromagnetic models on graphs

Thirty years ago, H. E. Stanley showed that an O(n) spin model on a lattice tends to a spherical model as n-->infinity. This means that at any temperature the corresponding free energies coincide. This fundamental result is no longer valid on more general discrete structures lacking in translation invariance, i.e., on graphs. However, only the singular parts of the free energies determine the critical behavior of the two statistical models. Here we show that for ferromagnetic models such singular parts still coincide even on graphs in the thermodynamic limit. This implies that the critical exponents of O(n) models on graphs for n-->infinity tend to the spherical ones and depend only on the graph spectral dimension.

Humoral immune response against hepatitis C virus.

Antibodies are in several instances a reliable marker indicating vigorous immune response against infectious agents and in several viral diseases presence in the blood of specific anti-viral antibodies indicates an effective protection. However, this is not always true. For example, in the case of hepatitis C virus (HCV) an important human pathogen considered the causative agent of the nonA- nonB hepatitis, in spite of an intense antibody response there is no protection against a new infection and in the majority of infected individuals the virus overcomes host defences establishing a persistent infection. Here we describe how the dissection of the humoral immune response against HCV glycoprotein E2 of infected patients was useful for a better comprehension of the virus-host interplay. Cross-reactive antibodies directed against E2 are produced by the HCV-infected patient, but not all of them are protective, and some could even result to be detrimental for the patient. The cross-reactive anti-HCV/E2 humoral antibody response is complex and not necessarily completely beneficial to the host.

Heterogeneity of the humoral anti-HCV/E2 response in persistently infected patients as demonstrated by divergent patterns of inhibition of the binding of anti-HCV/E2 human monoclonal antibodies.

A complete understanding of the molecular features of humoral immune response could be of pivotal importance in the management of persistent viruses as HCV. In this study, 24 HCV-positive samples, characterized by classical virological parameters, are evaluated using a new assay for the quantitation of antibody subpopulations directed against discrete epitopes on surface glycoprotein E2, a key viral protein. The results, besides confirming the usefulness of this new approach, highlight the extreme heterogeneity of anti-HCV/E2 response as far as single epitopes are concerned. The specific epitopes under study are also demonstrated to be widely shared among different genotypes.

A novel expression vector for production of epitope-tagged recombinant Fab fragments in bacteria.

Labeling of recombinant Fab molecules is an important yet cumbersome and time-consuming procedure that is needed in many immunological experimental designs. This work describes the development of a novel expression vector fusing to the carboxyterminal of the Fab heavy chain fragments a tag peptide (FLAG) that is consistently recognized by a mouse monoclonal antibody. The presence of the FLAG peptide does not alter the binding characteristics of the unmodified Fab molecule, as demonstrated by relative affinity determinations and competition experiments. This new method is suitable for extensive utilization in immunological experimental work using recombinant Fabs.

Localized states on comb lattices.

Complex networks and graphs provide a general description of a great variety of inhomogeneous discrete systems. These range from polymers and biomolecules to complex quantum devices, such as arrays of Josephson junctions, microbridges, and quantum wires. We introduce a technique, based on the analysis of the motion of a random walker, that allows us to determine the density of states of a general local Hamiltonian on a graph, when the potential differs from zero on a finite number of sites. We study in detail the case of the comb lattice and we derive an analytic expression for the elements of the resolvent operator of the Hamiltonian, giving its complete spectrum.

Diffusive thermal dynamics for the Ising ferromagnet.

We introduce a thermal dynamics for the Ising ferromagnet where the energy variations occurring within the system exhibit a diffusive character typical of thermalizing agents such as, e.g., localized excitations. Time evolution is provided by a walker hopping across the sites of the underlying lattice according to local probabilities depending on the usual Boltzmann weight at a given temperature. Despite the canonical hopping probabilities the walker drives the system to a stationary state which is not reducible to the canonical equilibrium state in a trivial way. The system still exhibits a magnetic phase transition occurring at a finite value of the temperature larger than the canonical one. The dependence of the model on the density of walkers realizing the dynamics is also discussed. Interestingly the differences between the stationary state and the Boltzmann equilibrium state decrease with increasing number of walkers.

Phage display for the production of human monoclonal antibodies against human pathogens.

In the last decade an increasing number of antibodies have made their way from the research benchtops into the clinics and many more are currently under clinical trial. Among monoclonal antibody-producing techniques, phage-display is undoubtedly the most effective and versatile. Cloning of the entire humoral repertoire derived from an infected patients into a phage display vector allows not only the simple generation of monoclonal antibodies of desired specificity, but also the molecular dissection of the antibody response itself. Generation of large panels of human monoclonal antibodies against human pathogens could open new perspectives in understanding the interplay between the infectious agent and the infected host providing tools for the prevention and the therapy of human communicable diseases. In this paper the basic principles of the phage-display approach as well as its most recent applications are reviewed.

Engineering human monoclonal antibody fragments: a recombinant enzyme-linked Fab.

A new plasmid vector, pCRP, allowing the expression of human recombinant monoclonal antibody Fab fragments fused with a bacterial acid phosphatase has been constructed. pCRP can accept heavy- and light-chain cDNAs cloned from combinatorial antibody libraries displayed on filamentous phages with the pCombIII system and is able to direct expression to soluble Fabs in which the carboxy-terminus of the heavy chain is fused to the amino-terminus of the mature PhoN nonspecific acid phosphatase of Providencia stuartii. Using the pCRP vector, we expressed two different human recombinant Fabs cloned from combinatorial libraries (one anti-tetenus toxoid and the other anti-HIV-1 gp120) fused with the acid phosphatase. In both cases chimeric antibodies were obtained which retained the antigen-binding ability and the enzymatic activity. Similar Fab-enzyme fusions can be successfully used, even unpurified, in enzyme immunoassays.

Cloning and characterization of human recombinant antibody Fab fragments specific for types 1 and 2 herpes simplex virus.

Twenty-six bacterial clones producing human recombinant Fab fragments specific for Herpes Simplex virus (HSV) antigens were obtained from an IgG1k human antibody combinatorial library displayed on filamentous phage, following panning against an HSV lysate. All the Fabs reacted against the HSV lysate in enzyme-linked immunosorbent assay and were able to recognize both type 1 and type 2 HSV in an indirect immunofluorescence assay (IFA). DNA sequencing of the heavy chain variable regions showed that these Fabs were different from those already described. One of these Fabs (Fab19) was purified and subjected to further characterization. Purified Fab19 was able to specifically recognize several different HSV-1 and HSV-2 strains (including 2 reference strains and 12 clinical isolates) in IFA. It was also able to neutralize the infectivity of both HSV-1 and HSV-2 strains, although the neutralizing activity was somewhat lower against HSV-2. In fact, 100% neutralization of infectivity was observed at a Fab concentration of 2 micrograms/100 TCD50 for the majority of HSV-1 strains, while a concentration of 8 micrograms/100 TCD50 was needed for 100% neutralization of all the HSV-2 strains tested. Owing to the above properties, Fab19 appears to be useful for diagnostic purposes and might also prove useful for in vivo immunoprophylaxis and therapy of HSV infections.

A new plasmid cloning vector for direct detection of recombinant clones, based on inactivation of a bacterial acid phosphatase-encoding gene.

A new plasmid cloning vector for Escherichia coli (pPhoR) suitable for direct detection of recombinant clones has been constructed. The plasmid is a multicopy of a vector which carries a pUC-derived origin of replication and beta-lactamase gene, and the phoN acid phosphatase-encoding gene from Providencia stuartii. Foreign DNA fragments can be cloned into unique restriction sites located within the phoN gene causing a loss of the acid phosphatase activity which is normally overproduced by E. coli strains carrying pPhoR. Since PhoN production can be easily detected by a plate histochemical assay, recombinant clones carrying foreign DNA fragments inserted in the phoN gene can be easily detected as PhoN-negative clolonies on the above medium. The efficiency of the pPhoR-based cloning system for direct cloning of PCR amplimers of a variable region of the HIV-1 genome was comparable to that of conventional cloning systems for direct detection of recombinant based on beta-galactosidase inactivation. Advantage of the pPho-R-based system include reduced costs for histochemical assays and the possibility of being used with any E. coli host.