Long-range interacting classical systems: universality in mixing weakening

Through molecular dynamics, we study the $d=2,3$ classical model of $N$ coupled rotators (inertial XY model) assuming a coupling constant which decays with distance as $r_{ij}^{-\alpha}$ ($\alpha \ge 0$). The total energy $$ is asymptotically $\propto N {\tilde N}$ with ${\tilde N} \equiv [N^{1-\alpha/d}-(\alpha/d)]/[1-\alpha/d]$, hence the model is thermodynamically extensive if $\alpha/d>1$ and nonextensive otherwise. We numerically show that, for energies above some threshold, the (appropriately scaled) maximum Lyapunov exponent is $\propto N^{-\kappa}$ where $\kappa$ is an {\it universal} (one and the same for $d=1,2$ and 3, and all energies) function of $\alpha/d$, which monotonically decreases from 1/3 to zero when $\alpha/d$ increases from 0 to 1, and identically vanishes above 1. These features are consistent with the nonextensive statistical mechanics scenario, where thermodynamic extensivity is associated with {\it exponential} mixing in phase space, whereas {\it weaker} (possibly {\it power-law} in the present case) mixing emerges at the $N \to \infty$ limit whenever nonextensivity is observed.Comment: 4 pages, 3 figures; Submitted to Physical Review Letter

The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years’ experience of association studies to understand the genetic architecture of pancreatic cancer

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groupsAssociazione Italiana per la Ricerca sul Cancro (AIRC) under IG 2019—ID. 23672 project—P.I. Campa Daniele and IG 2021 ID – 26201 project P.IThe Czech Ministry of Health, NU21–07–00247 and from Programme EXCELESID Project No. LX22NPO5102. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG)Italian Minister of Health, Ricerca Corrente program 2022–2024Cancer Research UK (C7690/A26881, C18616/A25153) and Pancreatic Cancer UK. Sample accrual at the Amsterdam UMC was supported by the AMC FoundationCOST Action TRANSPANCA21116COST (European Cooperation in Science and Technology

Metastable states in a class of long-range Hamiltonian systems

We numerically show that metastable states, similar to the Quasi Stationary States found in the so called Hamiltonian Mean Field Model, are also present in a generalized model in which $N$ classical spins (rotators) interact through ferromagnetic couplings decaying as $r^{-\alpha}$, where $r$ is their distance over a regular lattice. Scaling laws with $N$ are briefly discussed.Comment: Latex 2e, 11 pages, 3 eps figures, contributed paper to the conf. "NEXT 2001", 23-30 May 2001, Cagliari (Italy), submitted to Physica

Canonical solution of a system of long-range interacting rotators on a lattice

The canonical partition function of a system of rotators (classical X-Y spins) on a lattice, coupled by terms decaying as the inverse of their distance to the power alpha, is analytically computed. It is also shown how to compute a rescaling function that allows to reduce the model, for any d-dimensional lattice and for any alpha<d, to the mean field (alpha=0) model.Comment: Initially submitted to Physical Review Letters: following referees' Comments it has been transferred to Phys. Rev. E, because of supposed no general interest. Divided into sections, corrections in (5) and (20), reference 5 updated. 8 pages 1 figur

Track structure, radiation quality and initial radiobiological events: Considerations based on the PARTRAC code experience

Purpose: The role of track structures for understanding the biological effects of radiation has been the subject of research activities for decades. The physics that describes such processes is the core Monte Carlo codes, such as the biophysical PARTRAC (PARticle TRACks) code described in this review, which follow the mechanisms of radiation-matter interaction from the early stage. In this paper a review of the track structure theory (and of its possible extension concerning non-DNA targets) is presented. Materials and methods: The role of radiation quality and track structure is analyzed starting from the heavy ions results obtained with the biophysical Monte Carlo code PARTRAC (PARticles TRACks). PARTRAC calculates DNA damage in human cells based on the superposition of simulated track structures in liquid water to an ‘atom-by-atom’ model of human DNA. Results: Calculations for DNA fragmentation compared with experimental data for different radiation qualities are illustrated. As an example, the strong dependence of the complexity of DNA damage on radiation track structure, and the very large production of very small DNA fragments (lower than 1 kbp (kilo base pairs) usually not detected experimentally) after high LET (high-Linear Energy Transfer) irradiation is shown. Furthermore the possible importance of non-nuclear/non-DNA targets is discussed in the particular case of cellular membrane and mitochondria. Conclusions: The importance of the track structure is underlined, in particular the dependence of a given late cellular effect on the spatial distribution of DNA double-strand breaks (DSB) along the radiation track. These results show that the relative biological effectiveness (RBE) for DSB production can be significantly larger than 1. Moreover the cluster properties of high LET radiation may determine specific initial targets and damage evolution

Canonical Solution of Classical Magnetic Models with Long-Range Couplings

We study the canonical solution of a family of classical $n-vector$ spin models on a generic $d$-dimensional lattice; the couplings between two spins decay as the inverse of their distance raised to the power $\alpha$, with $\alpha<d$. The control of the thermodynamic limit requires the introduction of a rescaling factor in the potential energy, which makes the model extensive but not additive. A detailed analysis of the asymptotic spectral properties of the matrix of couplings was necessary to justify the saddle point method applied to the integration of functions depending on a diverging number of variables. The properties of a class of functions related to the modified Bessel functions had to be investigated. For given $n$, and for any $\alpha$, $d$ and lattice geometry, the solution is equivalent to that of the $\alpha=0$ model, where the dimensionality $d$ and the geometry of the lattice are irrelevant.Comment: Submitted for publication in Journal of Statistical Physic

GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis

Genetic variants; Multiple myeloma; ObesityVariantes genéticas; Mieloma múltiple; ObesidadVariants genètiques; Mieloma múltiple; ObesitatMultiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.This work was supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI17/02256 and PI20/01845), from the Consejería de Salud y Familia de la Junta de Andalucía (PY20/01282) and from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS (01ZX1309))

Bitter taste receptor polymorphisms and human aging.

Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics

Association between TAS2R38 gene polymorphisms and colorectal cancer risk

Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99-1.67; P(value) = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06-1.75; P(value) = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12-1.61; P(value) = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin