When--and how--can a cellular automaton be rewritten as a lattice gas?

Both cellular automata (CA) and lattice-gas automata (LG) provide finite algorithmic presentations for certain classes of infinite dynamical systems studied by symbolic dynamics; it is customary to use the term `cellular automaton' or `lattice gas' for the dynamic system itself as well as for its presentation. The two kinds of presentation share many traits but also display profound differences on issues ranging from decidability to modeling convenience and physical implementability. Following a conjecture by Toffoli and Margolus, it had been proved by Kari (and by Durand--Lose for more than two dimensions) that any invertible CA can be rewritten as an LG (with a possibly much more complex ``unit cell''). But until now it was not known whether this is possible in general for noninvertible CA--which comprise ``almost all'' CA and represent the bulk of examples in theory and applications. Even circumstantial evidence--whether in favor or against--was lacking. Here, for noninvertible CA, (a) we prove that an LG presentation is out of the question for the vanishingly small class of surjective ones. We then turn our attention to all the rest--noninvertible and nonsurjective--which comprise all the typical ones, including Conway's `Game of Life'. For these (b) we prove by explicit construction that all the one-dimensional ones are representable as LG, and (c) we present and motivate the conjecture that this result extends to any number of dimensions. The tradeoff between dissipation rate and structural complexity implied by the above results have compelling implications for the thermodynamics of computation at a microscopic scale.Comment: 16 page

Thermal treatment of bamboo with flame: influence on the mechanical characteristics

The mechanical properties of bamboo are susceptible to degradation due to both physical and biological agents. Among the non-chemical treatments, we studied the influence of a short-time heat treatment, using an LPG-gas torch, on the mechanical properties of a bamboo (Phyllostachys viridiglaucescens) growing in Italy. The response was very encouraging as we found no significant reduction in either elastic modulus or tensile, compressive and bending strength. Several samples were subject to tension, compression and bending tests to compare the responses of the treated and untreated culms. The average tensile elastic modulus was slightly greater for the untreated culms. The average tensile strength of the untreated culms was only slightly greater, and the differences can be assumed to be insignificant from a structural point of view. The average value of the treated culms compressive elastic modulus was slightly greater than that of the untreated ones. The compressive strength was essentially the same. The bending mechanical behaviour was barely influenced by the thermal treatment. A microscopic investigation (optical and electron microscopy) was undertaken to investigate the possible deterioration of the bamboo microstructure due to the heat treatment. No appreciable damage was detectable in the treated material. The proposed heat treatments can be considered as a reliable and sustainable protection practice for bamboo culms

Hybrid harmony search for sustainable design of post-tensioned concrete box-girder pedestrian bridges

This paper aims to find sustainable designs of post-tensioned concrete box-girder pedestrian bridges. A hybrid harmony search algorithm combining threshold optimization is used to find the geometry and the materials for which the sum of the costs or the emissions are the lowest, yet satisfying the requirements for structural safety and durability. An experimental design method was used to adjust the algorithm parameters. The parametric study was applied to three-span deck bridges ranging from 90 m to 130 m. The findings indicated that both objectives lead to similar cost results. However, the variables presented some differences. Such deviations suggested greater depths, more strands and a lower concrete strength for CO2 target functions. Carbonation captured less than 1% of the deck emissions over 100 years. This methodology leads to a precise analysis of the practical rules to achieve an environmental design approach.This research was financially supported by the Spanish Ministry of Science and Innovation (Research Project BIA2011-23602).García Segura, T.; Yepes Piqueras, V.; Alcalá González, J.; Pérez López, E. (2015). Hybrid harmony search for sustainable design of post-tensioned concrete box-girder pedestrian bridges. Engineering Structures. 92:112-122. https://doi.org/10.1016/j.engstruct.2015.03.015S1121229

Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

Background: Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging. Patients and methods: Here, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo 'stopwatch'. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively 'carbon date' the malignant progression. Results: The primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity. Conclusion: Our data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate

Current and novel therapeutic opportunities for systemic therapy in biliary cancer

none24Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.openMarin J.J.G.; Prete M.G.; Lamarca A.; Tavolari S.; Landa-Magdalena A.; Brandi G.; Segatto O.; Vogel A.; Macias R.I.R.; Rodrigues P.M.; Casta A.L.; Mertens J.; Rodrigues C.M.P.; Fernandez-Barrena M.G.; Da Silva Ruivo A.; Marzioni M.; Mentrasti G.; Acedo P.; Munoz-Garrido P.; Cardinale V.; Banales J.M.; Valle J.W.; Bridgewater J.; Braconi C.Marin, J. J. G.; Prete, M. G.; Lamarca, A.; Tavolari, S.; Landa-Magdalena, A.; Brandi, G.; Segatto, O.; Vogel, A.; Macias, R. I. R.; Rodrigues, P. M.; Casta, A. L.; Mertens, J.; Rodrigues, C. M. P.; Fernandez-Barrena, M. G.; Da Silva Ruivo, A.; Marzioni, M.; Mentrasti, G.; Acedo, P.; Munoz-Garrido, P.; Cardinale, V.; Banales, J. M.; Valle, J. W.; Bridgewater, J.; Braconi, C

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann\u2013Whitney U test for continuous variables. Results: A slight reduction ( 126.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop 1212% versus 123.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts

KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer

There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting

Current and novel therapeutic opportunities for systemic therapy in biliary cancer

Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools