Challenges and strategies in precision medicine for non-small cell lung cancer

Lung cancer is the most common cause of cancer- related death worldwide, causing over 1.2 million deaths each year. Non–small-cell lung cancer (NSCLC) consists of a group of malignancies that are pathologically and molecularly diverse but that are all characterised by a poor prognosis. Survival rates for lung cancer patients have improved very slowly and only to a modest degree owing partly to poor funding for research into this malignancy and stigma associated with smoking, as well as relative chemo-resistance. However, in recent years, NSCLC has become an exemplar for precision medicine, mainly following development of drugs targeting the receptors of epidermal growth factor and anaplastic lymphoma kinase. While epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors are only applicable to a minority of patients and benefits are almost invariably short-lived, current studies indicate that at least 50% of patients with NSCLC have a targetable mutation. With a growing armamentarium of inhibitors against these targets in development, there is a hope that a greater proportion of patients will benefit from precision medicine and that such benefits will be sustained. However, there remain significant challenges in the development of precision medicine in NSCLC. These include: identification and validation of new targets; ensuring biopsies are fit for purpose; tumour heterogeneity; requirements for serial tumour assessments; and not least cost. In this review, we will discuss the current status of precision medicine in NSCLC as well as how basic and translational research are paving the way towards overcoming the above challenges. In addition, we will pay attention to clinical strategies in respect to liquid biopsies and the potential use of extracellular vesicles such as exosomes in cancer therapeutics

Agricultura familiar e políticas públicas: o impacto do Pronaf no Rio Grande do Sul.

A aparição do Programa Nacional de Fortalecimento da Agricultura Familiar (PRONAF) marca um momento singular na trajetória do processo de intervenção estatal na agricultura e no mundo rural do Brasil. Apesar de avanços no aperfeiçoamento e ampliação do universo de cobertura, o programa permanece ancorado numa ambigüidade básica tanto em termos do público-alvo a ser beneficiado quanto aos objetivos essenciais que persegue, onde, na retórica oficial, mesclam-se orientações tipicamente produtivistas com compromissos mais amplos, como a geração de empregos, a inclusão social e o desenvolvimento territorial. O artigo em questão desenvolve uma análise do PRONAF à luz de recente pesquisa realizada no Estado do Rio Grande do Sul, inserida no contexto de um convênio firmado entre o PCT/IICA-PRONAF e a Fundação de Economia de Campinas - FECAMP para montar um sistema de acompanhamento das ações do Ministério do Desenvolvimento Agrário e avaliar os impactos deste programa. Os dados finais mostram fortes evidências de diferenciação social dentre os produtores familiares

A Soluble Free-Fermion Model in d Dimensions

We consider a vertex model in d dimensions characterized by lines which run in a preferred direction. We show that this vertex model is soluble if the weights of vertices with intersecting lines are given by a free-fermion condition, and that a fugacity -1 is associated to each loop of lines. The solution is obtained by mapping the model into a dimer problem and by evaluating a Pfaffian. We also determine the critical point and the singular behavior of the free energy.Comment: 19 pages, REVTEX, 6 figure

Diagnóstico do manejo do carrapato Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) no sistema de produção de pecuária familiar do Alto Camaquã.

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Ervas daninhas do Brasil. Solanaceae I. Gênero Solanum L.

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The association of food ingredients in breakfast cereal products and fumonisins production: risks identification and predictions

Breakfast processed products are remarkably at risk of fungal contamination. This research surveyed the fumonisins concentration in different breakfast products, and carried out in-vitro experiments measuring fumonisins content in different substrates inoculated with Fusarium verticillioides. The pipeline started with the identification of combinations of ingredients for 58 breakfast products. Twenty-three core ingredients, seven nutritional components and production types were analyzed using a Pearson correlation, k-means clustering and principal component analysis to show that no single factor is responsible for high fumonisins detection in processed cereals products. Consequently, decision tree regression was used as a means of determining and visualizing complex logical interactions between the same factors. We clustered the association of ingredients in low, medium, and high risk of fumonisin detection. The analysis showed that high fumonisins concentration is associated with those products that have high maize concentrations coupled especially with high sodium or rice. In a in-vitro experiment, different media were prepared by mixing the ingredients in the proportion found in the first survey and by measuring fumonisins production by Fusarium verticillioides. Results showed that: 1) fumonisins production by F. verticillioides is boosted by the synergistic effect of maize and highly ready carbohydrate content such as white flour; 2) a combination of maize >26%(w/w), rice >2.5%(w/w), NaCl >2.2%(w/w) led to high fumonisins production, while mono-ingredient products were more protective against fumonisins production. The observations in the in-vitro experiments appeared to align with the decision tree model that an increase in ingredient complexity can lead to fumonisins production by Fusarium. However, more research is urgently needed to develop the area of predictive mycology based on the association of processing, ingredients, fungal development, and mycotoxins production

Efficient CO2 electroreduction on tin modified cuprous oxide synthesized via a one-pot microwave-assisted route

Bimetallic copper-tin catalysts are considered cost-effective and suitable for large-scale electrochemical conversion of CO2 to valuable products. In this work, a class of tin (Sn) modified cuprous oxide (Cu2O) is simply synthesized through a one-pot microwave-assisted solvothermal method and thoroughly characterized by various techniques. Sn is uniformly distributed on the Cu2O crystals showing a cube-within-cube structure, and CuSn alloy phase emerges at high Sn contents. The atomic ratio of Cu to Sn is found to be crucially important for the selectivity of the CO2 reduction reaction, and a ratio of 11.6 leads to the optimal selectivity for CO. This electrode shows a high current density of 47.2 mA cm−2 for CO formation at −1.0 V vs. the reversible hydrogen electrode and also displays good CO selectivity of 80–90% in a wide potential range. In particular, considerable CO selectivity of 72–81% is achieved at relatively low overpotentials from 240 mV to 340 mV. During the long-term tests, satisfactory stability is observed for the optimal electrode in terms of both electrode activity and CO selectivity. The relatively low price, the fast and scalable synthesis, and the encouraging performance of the proposed material implies its good potential to be implemented in large-scale CO2 electrolyzers

First Report on the Benthic Invertebrate Community Associated With a Bronze Naval Ram From the First Punic War: A Proxy of Marine Biodiversity

Historical traces of organisms on the seafloor, such as shells and tubes, constitute the ecological memory of ancient benthic assemblages and serve as an important resource for understanding the assembly of modern communities. Archeological shipwrecks are particularly interesting submerged substrata for both their archeological and biological implications. For the first time, we studied the species composition and life-history traits of dominant organisms in the benthic assemblage on a bronze Carthaginian naval ram, which sank more than two thousand years ago in the Southern Tyrrhenian Sea. By comparing the species composition of the ram assemblage with those of the surrounding habitats, we inferred possible colonization patterns for the ram and discussed the informative role of the shipwreck as a proxy of marine biodiversity. The ram assemblage was rich in species, including both sessile (bryozoans, serpulid polychaetes, and few bivalves) and motile (gastropods) species. Sexual reproduction with free-spawning fertilization and long-duration larvae characterized most species. The long submersion time of the ram, together with the reproductive strategies, growth forms, and motility of the dominant species were key factors shaping the community of the ram. The ram itself offers an archeological artifact of inestimable value, but our analysis revealed it to be an effective collector of fauna from the surrounding seabed. The ram community hosted species from a range of nearby natural habitats (mostly coralligenous, detritic bottoms, and zoosteracean meadows) and thus served as a proxy for marine biodiversity on the surrounding seabed. We conclude that the presence of many species on the ram that commonly occur in adjacent habitats of great environmental value was informative and highlight the important marine biodiversity in the area of the Aegadian archipelago

The Gaia-ESO Survey: Separating disk chemical substructures with cluster models

(Abridged) Recent spectroscopic surveys have begun to explore the Galactic disk system outside the solar neighborhood on the basis of large data samples. In this way, they provide valuable information for testing spatial and temporal variations of disk structure kinematics and chemical evolution. We used a Gaussian mixture model algorithm, as a rigurous mathematical approach, to separate in the [Mg/Fe] vs. [Fe/H] plane a clean disk star subsample from the Gaia-ESO survey internal data release 2. We find that the sample is separated into five groups associated with major Galactic components; the metal-rich end of the halo, the thick disk, and three subgroups for the thin disk sequence. This is confirmed with a sample of red clump stars from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. The two metal-intermediate and metal-rich groups of the thin disk decomposition ([Fe/H]>-0.25 dex) highlight a change in the slope at solar metallicity. This holds true at different radial regions. The distribution of Galactocentric radial distances of the metal-poor part of the thin disk ([Fe/H]<-0.25 dex) is shifted to larger distances than those of the more metal-rich parts. Moreover, the metal-poor part of the thin disk presents indications of a scale height intermediate between those of the thick and the rest of the thin disk, and it displays higher azimuthal velocities than the latter. These stars might have formed and evolved in parallel and/or dissociated from the inside-out formation taking place in the internal thin disk. Their enhancement levels might be due to their origin from gas pre-enriched by outflows from the thick disk or the inner halo. The smooth trends of their properties (their spatial distribution with respect to the plane, in particular) with [Fe/H] and [Mg/Fe] suggested by the data indicates a quiet dynamical evolution, with no relevant merger events