Hyperactive Learning (HAL) for Data-Driven Interatomic Potentials

Data-driven interatomic potentials have emerged as a powerful class of surrogate models for {\it ab initio} potential energy surfaces that are able to reliably predict macroscopic properties with experimental accuracy. In generating accurate and transferable potentials the most time-consuming and arguably most important task is generating the training set, which still requires significant expert user input. To accelerate this process, this work presents \text{\it hyperactive learning} (HAL), a framework for formulating an accelerated sampling algorithm specifically for the task of training database generation. The key idea is to start from a physically motivated sampler (e.g., molecular dynamics) and add a biasing term that drives the system towards high uncertainty and thus to unseen training configurations. Building on this framework, general protocols for building training databases for alloys and polymers leveraging the HAL framework will be presented. For alloys, ACE potentials for AlSi10 are created by fitting to a minimal HAL-generated database containing 88 configurations (32 atoms each) with fast evaluation times of <100 microsecond/atom/cpu-core. These potentials are demonstrated to predict the melting temperature with excellent accuracy. For polymers, a HAL database is built using ACE, able to determine the density of a long polyethylene glycol (PEG) polymer formed of 200 monomer units with experimental accuracy by only fitting to small isolated PEG polymers with sizes ranging from 2 to 32.Comment: 21 pages, 11 figure

A kutyaszemélyiség mint az emberi személyiségvizsgálatok modellje: etológiai, pszichológiai és genetikai megközelítés = Dog personality as a model of the human personality: ethological, psychological and genetic investigations

Jelen pályázat célja a kutya személyiség modelljének kidolgozása volt, különös tekintettel az egyes személyiség komponensek esetleges genetikai meghatározottságára. A kutyák viselkedését 3 módszerrel elemeztük: (1) emberközpontú jellemzési kérdőív; (2) kutya viselkedését jellemző kérdőív; (3) közvetlen viselkedési megfigyelések (viselkedési tesztek). Mindhárom esetben sikerült többváltozós statisztikai elemzés segítségével (faktoranalízis) olyan modellt felállítani, amely jól leírja a kutyák személyiség dimenzióit, amely közül a többség az ember esetében is megtalálható. A SE Orvosvegytani Intézet munkatársai segítségével sikerült a dompamin 4-es receptorának polimorfizmusát számos kutyafajtában és farkasban kimutatni, és az egyes populációkat jellemezni, ami ember esetében is polimorf. Az ezt követő viselkedésgenetikai elemzés kimutatta, hogy mind a (rendőr) németjuhászkutyák esetében (aktivitás), mind a belgajuhászkutyák esetében (gazdára mutatott figyelem) létezik asszociáció a receptorgén adott allélja és a viselkedés között. Az elvégzett kutatás azt mutatja, hogy a kutya személyiség viselkedésen alapuló elemzése és a genetikai összefüggések kimutatása hasznos modellje lehet az ember személyiségnek. | The aim of the present research was to develop a personality model for the dog with regard to possible genetic influence. The behaviour of the dogs was analysed by the utilisation of three different methods: (1) anthropomorph questionnaires, (2) behaviour-directed questionnaires, (3) direct behavioural observations. By the use of multivariate statistical analysis (factor analysis) we were able to provide a behavioural model for the personality of dogs, which, shares some of its components with personality model obtained in the case of humans. In collaboration with the Semmelweis University we were able to provide evidence for the polymorphism of the DRD4 receptor in dogs, which is also the case in humans. Behaviour genetic analysis revealed that both in German shepherds police dogs (activity) and in Belgian shepherd dogs (attention toward the owner) there is association between behaviour and the presence of one type of allele. This research has provided encouraging evidence that the investigation of dog personality could be very fruitful model for human personality in the future

NANOPARTICLES: TOXICITY AND PENETRATION ACROSS BIOLOGICAL BARRIERS

Nanoparticles provide new opportunities for drug delivery and human therapy. To fulfill the therapeutical potential of nanoparticles two major aspects, toxicity and penetration across barriers of the body need to be studied. Different ex vivo and in vitro cell culture based models of the skin, nasal, lung, intestinal and blood-brain barriers have been established in our laboratory that can be used for both purposes. Three different types of nanoparticles were tested on the different models. Amorphous nanoparticles from the antiinflammatory drug meloxicam were obtained by by co-grinding with polyvinylpyrrolidone. Nanosized bilayered vesicles of non-ionic surfactants bearing glucose and amino acid ligands were prepared to specifically target solute carriers on the blood-brain barrier [1]. Poly(ferrocenyl silane) redox responsive polymer nanocarriers were also studied [2]. Several methods were applied parallelly to measure the toxicity of nanoparticles. In addition to colorimetric tests like MTT dye reduction assay, release of the cytoplasmic enzyme lactate dehydrogenase cellular events were also monitored in real time. By measuring impedance across microelectrodes covered with cells quantitative information on cell viability and intercellular adherence indicating paracellular permeability could be obtained. Co-culture models of the barriers prepared from primary cultures or human cell lines [3] served for permeability experiments to test the penetration of nanocarriers across cell layers. In the case of the blood-brain barrier a kinetic in vivo study in mice was also performed by near infrared fluorescence time-domain optical imaging. The results indicate that (i) toxicity measurements are very important to obtain the optimal dose of nanoparticles on living cells, (ii) nanonization of drugs can improve drug dissolution, absorption and pharmacokinetics, (iii) targeting of microvesicles increases their penetration across barriers