Life-Detection Technologies for the Next Two Decades

Since its inception six decades ago, astrobiology has diversified immensely to encompass several scientific questions including the origin and evolution of Terran life, the organic chemical composition of extraterrestrial objects, and the concept of habitability, among others. The detection of life beyond Earth forms the main goal of astrobiology, and a significant one for space exploration in general. This goal has galvanized and connected with other critical areas of investigation such as the analysis of meteorites and early Earth geological and biological systems, materials gathered by sample-return space missions, laboratory and computer simulations of extraterrestrial and early Earth environmental chemistry, astronomical remote sensing, and in-situ space exploration missions. Lately, scattered efforts are being undertaken towards the R&D of the novel and as-yet-space-unproven life-detection technologies capable of obtaining unambiguous evidence of extraterrestrial life, even if it is significantly different from Terran life. As the suite of space-proven payloads improves in breadth and sensitivity, this is an apt time to examine the progress and future of life-detection technologies.Comment: 6 pages, the white paper was submitted to and cited by the National Academy of Sciences in support of the Astrobiology Science Strategy for the Search for Life in the Univers

Long-Term Outcomes in Percutaneous Radiofrequency Ablation for Histologically Proven Colorectal Lung Metastasis

Introduction To evaluate the long-term outcome of image-guided radiofrequency ablation (RFA) when treating histologically confirmed colorectal lung metastasis in terms of overall survival (OS), progression-free survival (PFS) and local tumour control (LTC). Materials and Methods Retrospective single-centre study. Consecutive RFA treatments of histologically proven lung colorectal metastases between 01/01/2008 and 31/12/14. The primary outcome was patient survival (OS and PFS). Secondary outcomes were local tumour progression (LTP) and complications. Prognostic factors associated with OS/ PFS were determined by univariate and multivariate analyses. Results Sixty patients (39 males: 21 females; median age 69 years) and 125 colorectal lung metastases were treated. Eighty percent (n = 48) also underwent lung surgery for lung metastases. Mean metastasis size (cm) was 1.4 ± 0.6 (range 0.3–4.0). Median number of RFA sessions was 1 (1–4). During follow-up (median 45.5 months), 45 patients died (75%). The estimated OS and PFS survival rates at 1, 3, 5, 7, 9 years were 96.7%, 74.7%, 44.1%, 27.5%, 16.3% (median OS, 52 months) and 66.7%, 31.2%, 25.9%, 21.2% and 5.9% (median PFS, 19 months). The LTC rate was 90% with 6 patients developing LTP with 1-, 2-, 3- and 4-year LTP rates of 3.3%, 8.3%, 10.0% and 10.0%. Progression-free interval < 1 year (P = 0.002, HR = 0.375) and total number of pulmonary metastases (≥ 3) treated (P = 0.037, HR = 0.480) were independent negative prognostic factors. Thirty-day mortality rate was 0% with no intra-procedural deaths. Conclusion The long-term OS and PFS following RFA for the treatment of histologically confirmed colorectal lung metastases demonstrate comparable oncological durability to surgery

Computational Predictions of Amphiphile Aggregation for Early Compartmentalization

Extant biology uses a vast array of lipids to perform a range of tasks, and compartmentalization is critical for Life's existence by providing, a separation of chemical environments, enhanced local concentration of molecules, interfaces with reduced dimensionality, and individuality, leading to competition and evolution. We wished to explore and predict which kind of molecules are able to aggregate to form compartments that can host and/or encourage complex and perhaps even simple life-like chemistry that can be assayed easily in vitro. There may be a very large numberof such molecule types, and the use of high- resolution models is computationally prohibitive. We thus set out to develop an efficient way to predict aggregation and screen large in silico-generated compound libraries. There are a range of methods available for producing or accessing libraries of molecules. Through the recent explosion of lipidomics, there are a number of tools developed for mass spectrometry that include large compound libraries (e.g. LipidBlast, LipidHome, etc.). These give access to biologically relevant lipids, but do not facilitate the identification of novel molecules. We have identified computationally cheap methods for the generation of exhaustive lipid libraries and the evaluation of their propensity to self-assemble into either micelles or vesicles. Depending on user-defined parameters such libraries can easily contain well past trillions of molecules. We used MolGen (http://www.molgen.de/) for exhaustive generation of sub-libraries of lipid tails and heads. MolGen allows for disallowed molecular motifs and ranges of molecule parameters to be defined for the output. Once generated, solubility properties are assessed using QSPR models, and geometric properties computed. These are then combinatorially reacted using ChemAxon's Reactor software (https://chemaxon.com/) to give a final library. We finally evaluate them using chemoinformatics approaches to identify molecules that possess properties commensurate with an ability to form micelles, and more discriminatively, vesicles

Computational predictions of the aggregation of amphiphiles for early compartmentalisation

The formation of compartments, through which an internal environment is separated from its surrounding medium, is essential for all modern life. Compartmentalisation enables specific molecules to be concentrated, thus facilitating biochemistry. The existence of individuals also facilitates competition for survival, and provides a driving force for evolution. Modern cell membranes are incredibly complex structures, containing a myriad of lipid species, alongside various structural and functional proteins. However, protocells may not have had access to or required such a wide range of components to survive. Therefore the earliest membranes may have been composed of simple amphiphiles or simple mixtures of amphiphiles. A number of computationally intensive methods have proved ineffective at predicting the properties of these systems and so we developed chemoinformatics approaches to try to uncover the essential requirements for such molecules. Methods for generating compound libraries will be described as well as refinements to reduce the number of molecules generated or to control the similarity of the molecules to the known lipids of modern biology. The goal of this work is to understand which classes of simpler amphiphiles can self-assemble to form compartments and what the properties of the earliest membranes may have been. The limited molecular complexity of these amphiphiles may have enabled a variety of adaptive physical properties, such as enhanced permeability. Whilst this may compromise the level of protection from the external environment compared with modern biology, more permeable barriers could have facilitated more rapid introduction of greater diversity of chemical species and process. The generation of a novel large-scale library provides excellent coverage of chemical space, and the characterisation of these molecules provides insight into the aggregation properties of these chemical species

Computational Exploration of Lipid Chemical Space: Predicting Assembly Using QSPR Models

Compartmentalization is likely to have been essential for the emergence of life. Compartmentalization allows for the creation of unique chemical conditions that can be maintained out of equilibrium with the environment and the exclusion of parasites. Confining organic molecules also helps limit diffusion, increases concentration and can thus influence both the thermodynamics and kinetics of prebiotic reactions. Biology currently predominantly uses phospholipids to construct cell membranes. However, there are many other types of organic compounds that can form stable compartments in water, and many of these may have been abundant in the prebiotic environment. In this study we explore this alternative lipid chemical space by using structure enumeration algorithms to compute an exhaustive combinatorial library of surfactant molecules. We then predict the propensity of these compounds to self-assemble into membranes using quantitative structure-property relationship (QSPR) models on critical micelle concentration (CMC). Combined with critical packing parameter calculations, these models can allow identification of novel molecule types which can be experimentally assayed as candidates for the emergence of protocells

Adaptive properties of the genetically encoded amino acid alphabet are inherited from its subsets

Life uses a common set of 20 coded amino acids (CAAs) to construct proteins. This set was likely canonicalized during early evolution; before this, smaller amino acid sets were gradually expanded as new synthetic, proofreading and coding mechanisms became biologically available. Many possible subsets of the modern CAAs or other presently uncoded amino acids could have comprised the earlier sets. We explore the hypothesis that the CAAs were selectively fixed due to their unique adaptive chemical properties, which facilitate folding, catalysis, and solubility of proteins, and gave adaptive value to organisms able to encode them. Specifically, we studied in silico hypothetical CAA sets of 3–19 amino acids comprised of 1913 structurally diverse α-amino acids, exploring the adaptive value of their combined physicochemical properties relative to those of the modern CAA set. We find that even hypothetical sets containing modern CAA members are especially adaptive; it is difficult to find sets even among a large choice of alternatives that cover the chemical property space more amply. These results suggest that each time a CAA was discovered and embedded during evolution, it provided an adaptive value unusual among many alternatives, and each selective step may have helped bootstrap the developing set to include still more CAAs.</p

Life-Detection technologies for the next two decades

Since its inception six decades ago, astrobiology has diversified immensely to encompass several scientific questions including the origin and evolution of Terran life, the organic chemical composition of extraterrestrial objects, and the concept of habitability, among others. The detection of life beyond Earth forms the main goal of astrobiology, and a significant one for space exploration in general. This goal has galvanized and connected with other critical areas of investigation such as the analysis of meteorites and early Earth geological and biological systems, materials gathered by sample-return space missions, laboratory and computer simulations of extraterrestrial and early Earth environmental chemistry, astronomical remote sensing, and in-situ space exploration missions. Lately, scattered efforts are being undertaken towards the R&amp;D of the novel and as-yet-space-unproven life-detection technologies capable of obtaining unambiguous evidence of extraterrestrial life, even if it is significantly different from Terran life. As the suite of space-proven payloads improves in breadth and sensitivity, this is an apt time to examine the progress and future of life-detection technologies

Impacto orcamentario da utilizacao do Metodo Canguru no cuidado neonatal

OBJETIVO Estimar o impacto orçamentário da utilização do Método Canguru na rede municipal de saúde. MÉTODOS Um modelo de decisão analítico foi desenvolvido para simular os custos do Método Canguru e Unidade Intermediária Neonatal no Rio de Janeiro, RJ, em 2011. A população de referência foi constituída pelos recém-nascidos estáveis clinicamente, que podem receber assistência nas duas modalidades de cuidado. O impacto orçamentário foi estimado para uma coorte hipotética de 1.000 recém-nascidos elegíveis em um ano. A proporção de recém-nascidos elegíveis que recebem assistência nas duas modalidades foi obtida por coleta de dados nas maternidades incluídas no estudo. As probabilidades dos eventos e o consumo de recursos de saúde, no período da assistência, foram incorporados ao modelo. Cenários foram desenvolvidos para refletir a adoção do método Canguru em maior ou menor escala. RESULTADOS A utilização do Método Canguru significou redução de gastos equivalente a 16% em um ano, se todos os recém-nascidos elegíveis fossem assistidos por esse método. CONCLUSÕES A opção Método Canguru é de menor custo comparado com a da Unidade Intermediária Neonatal. A análise de impacto orçamentário da utilização desse método no Sistema Único de Saúde indicou economia importante para o período de um ano