A stochastic-hydrodynamic model of halo formation in charged particle beams

The formation of the beam halo in charged particle accelerators is studied in the framework of a stochastic-hydrodynamic model for the collective motion of the particle beam. In such a stochastic-hydrodynamic theory the density and the phase of the charged beam obey a set of coupled nonlinear hydrodynamic equations with explicit time-reversal invariance. This leads to a linearized theory that describes the collective dynamics of the beam in terms of a classical Schr\"odinger equation. Taking into account space-charge effects, we derive a set of coupled nonlinear hydrodynamic equations. These equations define a collective dynamics of self-interacting systems much in the same spirit as in the Gross-Pitaevskii and Landau-Ginzburg theories of the collective dynamics for interacting quantum many-body systems. Self-consistent solutions of the dynamical equations lead to quasi-stationary beam configurations with enhanced transverse dispersion and transverse emittance growth. In the limit of a frozen space-charge core it is then possible to determine and study the properties of stationary, stable core-plus-halo beam distributions. In this scheme the possible reproduction of the halo after its elimination is a consequence of the stationarity of the transverse distribution which plays the role of an attractor for every other distribution.Comment: 18 pages, 20 figures, submitted to Phys. Rev. ST A

Levy-Student Distributions for Halos in Accelerator Beams

We describe the transverse beam distribution in particle accelerators within the controlled, stochastic dynamical scheme of the Stochastic Mechanics (SM) which produces time reversal invariant diffusion processes. This leads to a linearized theory summarized in a Shchr\"odinger--like (\Sl) equation. The space charge effects have been introduced in a recent paper~\cite{prstab} by coupling this \Sl equation with the Maxwell equations. We analyze the space charge effects to understand how the dynamics produces the actual beam distributions, and in particular we show how the stationary, self--consistent solutions are related to the (external, and space--charge) potentials both when we suppose that the external field is harmonic (\emph{constant focusing}), and when we \emph{a priori} prescribe the shape of the stationary solution. We then proceed to discuss a few new ideas~\cite{epac04} by introducing the generalized Student distributions, namely non--Gaussian, L\'evy \emph{infinitely divisible} (but not \emph{stable}) distributions. We will discuss this idea from two different standpoints: (a) first by supposing that the stationary distribution of our (Wiener powered) SM model is a Student distribution; (b) by supposing that our model is based on a (non--Gaussian) L\'evy process whose increments are Student distributed. We show that in the case (a) the longer tails of the power decay of the Student laws, and in the case (b) the discontinuities of the L\'evy--Student process can well account for the rare escape of particles from the beam core, and hence for the formation of a halo in intense beams.Comment: revtex4, 18 pages, 12 figure

L\'evy-Schr\"odinger wave packets

We analyze the time--dependent solutions of the pseudo--differential L\'evy--Schr\"odinger wave equation in the free case, and we compare them with the associated L\'evy processes. We list the principal laws used to describe the time evolutions of both the L\'evy process densities, and the L\'evy--Schr\"odinger wave packets. To have self--adjoint generators and unitary evolutions we will consider only absolutely continuous, infinitely divisible L\'evy noises with laws symmetric under change of sign of the independent variable. We then show several examples of the characteristic behavior of the L\'evy--Schr\"odinger wave packets, and in particular of the bi-modality arising in their evolutions: a feature at variance with the typical diffusive uni--modality of both the L\'evy process densities, and the usual Schr\"odinger wave functions.Comment: 41 pages, 13 figures; paper substantially shortened, while keeping intact examples and results; changed format from "report" to "article"; eliminated Appendices B, C, F (old names); shifted Chapters 4 and 5 (old numbers) from text to Appendices C, D (new names); introduced connection between Relativistic q.m. laws and Generalized Hyperbolic law

Language Models as Knowledge Bases?

Recent progress in pretraining language models on large textual corpora led to a surge of improvements for downstream NLP tasks. Whilst learning linguistic knowledge, these models may also be storing relational knowledge present in the training data, and may be able to answer queries structured as "fill-in-the-blank" cloze statements. Language models have many advantages over structured knowledge bases: they require no schema engineering, allow practitioners to query about an open class of relations, are easy to extend to more data, and require no human supervision to train. We present an in-depth analysis of the relational knowledge already present (without fine-tuning) in a wide range of state-of-the-art pretrained language models. We find that (i) without fine-tuning, BERT contains relational knowledge competitive with traditional NLP methods that have some access to oracle knowledge, (ii) BERT also does remarkably well on open-domain question answering against a supervised baseline, and (iii) certain types of factual knowledge are learned much more readily than others by standard language model pretraining approaches. The surprisingly strong ability of these models to recall factual knowledge without any fine-tuning demonstrates their potential as unsupervised open-domain QA systems. The code to reproduce our analysis is available at https://github.com/facebookresearch/LAMA

Hábitos de consumo e aceitação da aparência de feijão guandu (Cajanus cajan (L.) Millsp.).

O feijão guandu é uma leguminosa cultivada em climas tropicais e subtropicais, sendo resistente à seca, rico em proteínas, muito utilizado como forrageira para alimentação de animais, possuindo potencial para alimentação humana

Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles

Chloro(triethylphosphine)gold(I), (Et(3)PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et(3)PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et(3)PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et(3)PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et(3)PAuCl (nano-Et(3)PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et(3)PAuCl, was clearly documented. The implications of these findings are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10534-021-00313-0

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

<p>Abstract</p> <p>Background</p> <p>Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells.</p> <p>Methods</p> <p>During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments.</p> <p>Results</p> <p>Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3⁺cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.</p> <p>Conclusions</p> <p>A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3⁺T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.</p> <p>Trail Registration</p> <p>ClinicalTrials.gov Identifier: NCT00705640</p

MiniHack the Planet: A Sandbox for Open-Ended Reinforcement Learning Research

Progress in deep reinforcement learning (RL) is heavily driven by the availability of challenging benchmarks used for training agents. However, benchmarks that are widely adopted by the community are not explicitly designed for evaluating specific capabilities of RL methods. While there exist environments for assessing particular open problems in RL (such as exploration, transfer learning, unsupervised environment design, or even language-assisted RL), it is generally difficult to extend these to richer, more complex environments once research goes beyond proof-of-concept results. We present MiniHack, a powerful sandbox framework for easily designing novel RL environments. MiniHack is a one-stop shop for RL experiments with environments ranging from small rooms to complex, procedurally generated worlds. By leveraging the full set of entities and environment dynamics from NetHack, one of the richest grid-based video games, MiniHack allows designing custom RL testbeds that are fast and convenient to use. With this sandbox framework, novel environments can be designed easily, either using a human-readable description language or a simple Python interface. In addition to a variety of RL tasks and baselines, MiniHack can wrap existing RL benchmarks and provide ways to seamlessly add additional complexity

KILT: a Benchmark for Knowledge Intensive Language Tasks.

Challenging problems such as open-domain question answering, fact checking, slot filling and entity linking require access to large, external knowledge sources. While some models do well on individual tasks, developing general models is difficult as each task might require computationally expensive indexing of custom knowledge sources, in addition to dedicated infrastructure. To catalyze research on models that condition on specific information in large textual resources, we present a benchmark for knowledge-intensive language tasks (KILT). All tasks in KILT are grounded in the same snapshot of Wikipedia, reducing engineering turnaround through the re-use of components, as well as accelerating research into task-agnostic memory architectures. We test both task-specific and general baselines, evaluating downstream performance in addition to the ability of the models to provide provenance. We find that a shared dense vector index coupled with a seq2seq model is a strong baseline, outperforming more tailor-made approaches for fact checking, open-domain question answering and dialogue, and yielding competitive results on entity linking and slot filling, by generating disambiguated text. KILT data and code are available at https://github.com/facebookresearc

po 317 a novel bispecific antibody to harness the herg1 β1 macromolecular complex for cancer therapy

Introduction Among hindrances in cancer treatment, the lack of appropriate markers to be exploited for targeted therapy, and the need of new potential drugs are two big challenges.hERG1 potassium channels area novel class of oncological targets and one of the most intriguing aspects of their involvement in tumour establishment and progression is the interaction with adhesion molecules, such as integrins. It has been recently demonstrated that macromolecular complexes formed between hERG1 and β1 integrins selectively occurs in many types of cancer (Becchetti A et al., 2017). In this scenario, hERG1 could be exploited as a therapeutic target providing non cardiotoxic strategies aimed at blocking hERG1. Material and methods A scDb, a bifunctional single-chain diabody, directed against hERG1/β1 complex, was developed via SOE-PCR methodology. Such antibody was tested on HCT116 cells in lateral motility and western blotting experiments. Moreover immunohistochemistry (IHC) was performed on metastatic colorectal cancer (mCRC) paraffin embedded samples using the scDb, an anti-hERG1 and an anti-b1 integrin. Results and discussions Performing IHC on sequential sections of mCRC confirmed the specificity of the scDb for both hERG1 and b1 integrin. In vitro data provide evidences that the administering of the bispecific antibody has an impact on lateral motility. Moreover, signalling pathways are also affected by the antibody treatment, as AKT phosphorylation and HIF1α levels are decreased when the molecule is administered.Such findings might suggest a possible effect of the bispecific antibody on the VEGF-A signalling pathway, which are consistent with our previous hypothesis (Becchetti A et al., 2017) of a possible cross-talk leading to a deep impact on VEGF expression and, thus, on neoangiogenesis. Conclusion scDb-hERG1/β1 could be used as a potential new treatment for cancer patients and as an early molecular diagnostic marker. In fact, the selective expression of hERG1/β1 complex in cancer cells and its role in angiogenesis and cancer progression suggests that a molecule selectively targeting the complex will be an invaluable tool for cancer treatment